(*) Corresponding authors : Jean Loup Huret and Philippe Dessen (*) Corresponding authors : Philippe Dessen
This "Deep Insight", is a general review article and summary on Internet databases for cytogeneticists, with hyperlinks to two more detailed review articles: General resources in Genetics and/or Oncology and Cancer Cytogenomics resources, completed by a tutorial: Practical Exercices.
The need for organising data bank
1981: Human Genome Mapping
1983: Catalog of Chromosome Aberrations in Cancer
1997: Atlas of Genetics and Cytogenetics in Oncology and Haematology
Recent reviews on cancer databases
2. GENERAL RESOURCES
III- Nucleic acid, genes and protein databases
V- Genome cartography
VI- Structural variation databases
VII- Polymorphism databases
VIII- Portals/Working consortiums
IX- Impact on diseases
XI- Cancer Registries
XII- Patient associations and interfaces between science and patients - freely accessible
3. CYTOGENOMICS RESOURCES
I- Chromosome rearrangements/Hybrid genes
4. PRACTICAL EXERCISE
Databases devoted stricto sensu to cancer cytogenetics are the "Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer" (http://cgap.nci.nih.gov/Chromosomes/Mitelman), the "Atlas of Genetics and Cytogenetics in Oncology and Haematology" (http://atlasgeneticsoncology.org), and COSMIC (http://cancer.sanger.ac.uk/cosmic). However, cancer being a complex multi-step process, cytogenetics are broaden to "cytogenomics", with complementary resources, including resources on proteins and cancer. These resources are essential to both practical and theoretical knowledge in cytogenomics of cancer. Must be briefly reviewed: general databases (nucleic acid and protein sequences databases and bibliographic ones), cancer genomic portals associated to recent international integrated programs, such as TCGA or ICGC, fusion genes databases, genomic sequences and transcripts databases (with different cartography browsers), array CGH databases and structural variation databases for copy number, polymorphisms and mutation databases, databases on proteins (structure and function with implication of mutations and rearrangements), databases on diseases, databases and books on pathology, cancers, and patient associations and interfaces between science and patients. Other resources such as the International System for Human Cytogenetic Nomenclature (ISCN), the International Classification of Diseases for Oncology (ICD-O), the Human Gene Nomenclature Database (HGNC), and the Nomenclature for the description of sequence variations allow a common language. Data within the scientific/medical community should be freely available. However, most of the institutional stakeholders are now gradually disengaging, and well known databases are forced to beg or to disappear (which may happen!).
Key words: Cytogenetic, Cancer, Database, Mitelman Database, Atlas of Genetics and Cytogenetics in Oncology and Haematology, COSMIC, PubMed, GenBank, TCGA, ICGC, UniProt, OMIM, IARC, ISCN, ICD-O, HGNC.
In each cancer case there is a genetic event present (Stratton MR et al., 2009). Cytogenetics has been a major player in understanding genetics behind cancer, providing specific keys for diagnosis and prognostic assessments, as well as enabling the sub-classification of otherwise seemingly identical disease entities (Mertens F et al., 2015). This "Deep Insight is dedicated to cytogenetics resources will highlight the various facets used in the current strategies in theoretical understanding of cancer and the consequent practical strategies in treating the disease.
In 1914, Boveri stated that the heritable acquired characteristics of cancer cells are brought about by a disturbance of the normal chromosomal balance (Boveri, 1914). This theory was supported by a wealth of experimental data showing that cancer originates in a single cell through acquired genetic changes. The investigation in the 1950s, on ascites tumors that were induced experimentally or observed in patients tended to confirm that cytogenetic aberrations are an important and integral part of tumor development and evolution. These cytogenetic studies demonstrated that certain laws could direct neoplasia-associated chromosomal variability. Like selective pressures, where any changes in the surrounding tumor would modify the equilibrium, causing a change where the most viable chromosomal profile is prevailing in the new environment.
The importance of cytogenetics boomed since the discovery of the first chromosomal anomaly reported by Peter Nowell and David Hungerford in 1960, linking the Philadelphia (Ph) chromosome to chronic myeloid leukaemia (CML) (Nowell and Hungerford, 1960). It was the first assessment in detecting chromosomal anomaly in human leukaemia and seemed reasonable that it was the cause of origin for CML. This discovery was the first strong assessment to Boveris theory. This observation stimulated the field to find other karyotypic anomalies in other cancers. Unfortunately, a heterogenous panel of chromosomal rearrangements was detected in what seemed to be the same cancer. This was a terrible setback for the arguments stating karyotypic anomalies as the origin of cancer. The explanation was that chromosomal rearrangements were an epiphenomenon that could appear during tumor progression without having any pathogenetic consequences.
In the 1970's the situation changed dramatically when chromosomal banding techniques invented by Caspersson and Zech (Caspersson T et al., 1970) were introduced. This process gave an option to identify individual chromosomes, which were defined by a unique banding pattern. The description of chromosomal rearrangements immediately became clearer providing more gravity to the conclusions drawn. This was a new era for cancer cytogenetics showing an increase in the numbers of aberrant human malignant and benign karyotypes.
In the 1980s, the onset of molecular genetics techniques intensely widened our understanding of the pathogenetic progression underlying the neoplastic process. These techniques provided an opportunity to characterise the chromosomal breakpoints at the molecular level and has highlighted two classes of genes implicated in these karyotypical rearrangements: the oncogenes and the tumor suppressing genes.
MYC and BCR/ABL1: One of the first oncogenes described as activated by chromosomal rearrangement is MYC, which was characterised in Burkitt lymphoma studies.
Another example is the translocation between ABL1 and BCR. Peter Nowell and David Hungerford first described a recurrent presence of an extra-chromosome in CML patients in 1960 (Nowell PCH and Hungerford DA, 1960). In 1973 Janet D. Rowley used quinacrine coloration to prove this chromosome to be the result of a translocation between chromosomes 9 and 22 (Rowley JD, 1973a). Only as late as 1982 de Klein et al. showed that the genes ABL1 and BCR were fused together giving rise to an abnormal gene (de Klein A et al., 1982). With these new techniques, each chromosome and chromosome region could be identified on the basis of their unique banding pattern, giving daylight to previously undetectable subtle rearrangements. By this technique she identified the recurrent translocation t(8;21)(q22;q22) (Rowley JD, 1973b). These findings evoked interest in the cytogenetic analysis of other haematological malignancies. The number of reported balanced rearrangements has increased, in particular translocations including t(8;14)(q24;q32), t(2;8)(p11;q24) and t(8;22)(q24;q11) in Burkitt lymphoma (Zech L et al., 1976 ; Berger R et al., 1979 ; Miyoshi I et al., 1979 ; Van Den Berghe H et al., 1979 ), t(4;11)(q21;q23) in acute lymphoblastic leukaemia (ALL) (Oshimura M et al., 1977 ) t(15;17)(q22;q21) in acute promyelocytic leukaemia (APL) (Rowley JD et al., 1977), and t(14;18)(q32;q21) in follicular lymphoma (Rowley JD et al., 1977). During this fruitful period the first specific translocation in an animal model was found, a mouse plasmacytoma, which is a B cell malignancy displaying similar characteristics to human Burkitt lymphomas (Ohno S et al., 1979).
The following decade witnessed a rise in number of results from malignant solid tumors, mainly sarcomas but also a few carcinomas. Several of the aberrations identified were as specific as the ones that were previously described in haematological cancer: t(2;13)(q36;q14) in alveolar rhabdomyosarcoma (ARMS) (Seidal T et al., 1982), t(11;22)(q24;q12) in Ewing sarcoma (Aurias A et al., 1983 ; Turc-Carel C et al., 1983), t(X;1)(p11;q21) in Kidney cancer (de Jong B et al., 1986) and t(6;9)(q23;p23) in alivary gland tumors (ACC) of the salivary glands (Stenman G et al., 1986). Evidence was showing that many benign tumors were bearing characteristic rearrangements, including reciprocal translocations such as t(3;8)(p21;q12) in salivary gland adenoma (SGA) (Mark J et al., 1980) and t(3;12)(q27;q13) in lipoma (Heim S et al., 1986 ; Turc-Carel C et al., 1986).
Although the vast majority of fusion genes are formed by balanced translocations, they can also be produced by interstitial deletions. These were first identified in the 1990s, amongst them the fusion between genes STIL (STIL/TAL1 interrupting locus) in T-ALL (Bernard O et al., 1991). Since then, many others where observed with more or less extensive deletions, duplications and/or amplifications in the breakpoint regions (Barr FG et al., 1996 ; Simon MP et al., 1997 ; Sinclair PB et al., 2000 ; Müller E et al., 2011). Gene fusion can also arise from copy number shifts like in the aforementioned fusion gene USP16/RUNX1 (ubiquitin specific peptidase 16 and runt related transcription factor 1) in chronic myelomonocytic leukemia (Gelsi-Boyer V et al., 2008) and in the fusion gene SET/NUP214 (SET nuclear proto-oncogene and nuclear pore complex protein Nup214) in T-ALL (Van Vlierberghe P et al., 2008 ; Mullighan CG et al., 2009 ; Santo EE et al., 2012 ; Plaszczyca A et al., 2014) (Figure 1).
Figure 1: Timeline of important discoveries concerning fusion genes, chromosomal rearrangements and the establishment of databases regrouping all these chromosomal abnormalities. For comments and suggestions or contributions, please contact us
In the late 1970s, various technical developments helped in solving what molecular consequences the oncogenic chromosomal rearrangements could have. These techniques enabled the identification and characterisation of genes that were located at the breakpoints of chromosomal rearrangements. The genes implicated in MPC, Burkitt lymphoma and CML proved to be pivotal for the comprehension of the mechanism underlying chromosomal rearrangements. The engineering of fluorescence in-situ hybridization (FISH) enabled several chromosomal structures to be identified simultaneously. This significantly improved the location of breakpoints on chromosomes. It also considerably reduced the scale of which chromosomes could be observed and broadened the type of rearrangements that could be observed (cryptic rearrangements). The big advantage of the FISH technique is that it can also be used for non-dividing cells (interphase nuclei). FISH probes of a specific gene can identify new partner genes, like in the case of mixed lineage leukemia (MLL, KMT2A) gene (De Braekeleer E et al., 2009; Meyer C et al., 2013).
Although cytogenetic analyses are unquestionably crucial for the identification of fusion genes and rearrangements, there are certain limits to this technique. Firstly, revealing chromosome bandings requires having access to in-vitro living, dividing cells so that metaphases can be observed. Secondly, some tumor types can have very complex genomes which makes it difficult to understand the full story and distinguish the primary aberrations and origin of the cancer development from the bulk of the rearrangements (Speicher MR and Carter NP, 2005).
In the 1990s, the progress of high throughput tools for global genetic analyses, such as array based platforms for gene expression and copy number profiling, gave rise to new methods for observing chromosomal rearrangements. These techniques were not ideal either since balanced chromosomal rearrangements could pass undetected or the analysis of expression profiles could prove to be tricky. On the other hand, they presented a higher level of resolution than in chromosome banding and didn't require prior cell culturing (Pinkel D and Albertson DG, 2005; De Braekeleer E et al., 2014). The first novel gene fusion detected with the analysis of gene expression pattern of a tumor was the fusion of the transcription factor PAX3 gene with the nuclear receptor co-activator 1, NCOA1 gene. By focusing on genes presenting outlined values of expression, the fusions genes implicating the transmembrane protease serine 2 gene (TMPRSS2) with two genes encoding ETS transcription factors. The first is v-ets avian erythroblastosis virus E26 oncogene homolog (ERG) and the second is ets variant 1 (ETV1) (Tomlins SA et al., 2005). It was the first report of specific fusion genes implicated and representing a major subset of a common epithelial malignancy. By using a modification of this method, other fusion genes were discovered in many tumor types, such as tenosynovial giant cell tumor, lung cancer and chondrosarcoma (West RB et al., 2006; Rikova K et al., 2007; Soda M et al., 2007; Wang L et al., 2012).
The introduction of deep sequencing technologies a few years ago gave a new insight to identify new fusions genes either at DNA or RNA level. The combination of detailed information (base pair level) and broad (genome-wide) on DNA, transcriptome, structural variants and fusion transcripts could be obtained without any prior information on the cytogenetic features of the cancer cells. The initial study using deep sequencing to detect fusion genes or chromosomal rearrangements were done on established cell lines (Campbell PJ et al., 2008). The analysis of primary samples from common cancer (Maher CA et al., 2009a; Maher CA et al., 2009b), such as carcinomas of the breast (Stephens PJ et al., 2009), colon (Cancer Genome Atlas Research Network, 2013), lung (Cancer Genome Atlas Research Network, 2012), prostate (Cancer Genome Atlas Research Network, 2014), uterus ( Cancer Genome Atlas Research Network et al., 2013) as well as leukaemias and lymphomas (Steidl C et al., 2011 ; Welch JS et al., 2011 ; Roberts KG et al., 2012), came afterward. One study draws a bridge between over several several cancers by cumulating the bioinformatics data of 4,366 cancers from 13 different tumor types that were previously studied within the Cancer Genome Atlas (TCGA) network. The outcome was the description of 8,600 different fusion transcripts (Yoshihara K et al., 2015). These results have dramatically changed the gene fusion landscape with the identification of more than 10,000 fusion genes with more than 90% of these having been identified by various deep-sequencing approaches during the last 5 years (Mitelman F et al, 2016; Huret JL et al., 2013).
The high resolution of deep sequencing gave the possibility to identify the vast majority of genes implicated in chromosomal rearrangements that would have been complicated or impossible to identify by conventional cytogenetic techniques. Indeed, 75% of the genes fusions first detected by deep sequencing are intrachromosomal and approximately 50% are between genes located in the same chromosome band (Mitelman F et al, 2016). Large majority of genes, - already described in the literature before the deep sequencing era- were embedded in extensive networks like MLL in leukaemias, EWS RNA-binding protein 1 (EWSR1) in sarcomas and rearranged during Transfection Protooncogene (RET) in carcinomas (Mitelman F et al., 2007). However, this picture has somewhat changed with the massive increase of fusion genes that were added with genome-wide studies. The fact that these studies were mainly focusing on previously uncharacterized tumor types brought a lot of new networks emerging from rarer gene fusions than leukaemias, lymphomas and sarcomas. Furthermore, carcinomas often show highly rearranged genomes, with numerous mutations at the gene and chromosome levels and it may be that the genes detected by deep sequencing are the results of chance events caused by chromosomal instability, as vast majority of fusion transcripts were associated with amplification or deletion events at the DNA level (Yoshihara K et al., 2015; Mitelman H et al, 2016; Huret JL et al., 2013; Mitelman F et al., 2007; Kalyana-Sundaram S et al., 2012). Transcription-induced gene fusion (TIGF) or Trans-TIGF, when they happen on different chromosomes, results in the fusion of transcripts from non-adjacent genes without a corresponding fusion at DNA level (Gingeras TR, 2009; Rickman DS et al., 2009; Meyer C et al., 2009 ; Hedegaard J et al., 2014). Certain have been shown to have no impact, since they were expressed in normal tissues like the fusion genes JAZF zinc finger 1 (JAZF1)/SUZ12 a polycomb repressive complex 2 subunit and PAX3/
The prognostic and treatment value of chromosomal rearrangements and mutated genes: The high correlation between recurrent gene fusions and tumor subtypes has made them the ideal maker for diagnostic purposes. This correlation is also important in treatment stratification, the best example being the different fusion of MLL in AML (Meyer C et al., 2009). The routine molecular strategy to detect these fusion genes is the use of cytogenetics, FISH, RT-PCR and deep sequencing. The mounting knowledge of the clinical importance of gene fusions, as well as various chromosomal rearrangements, has gradually led to an increasing emphasis on genetic features in the classification of tumors. The latest World Health Organisation (WHO) classification, translocation and/or gene fusion status is mandatory for the diagnosis of some types of tumors, such as "AML with t(8;21)(q22;q22), RUNX1/RUNX1T1" and "B lymphoblastic leukaemia/lymphoma with t(5;14)(q31;q32), IL3/IGH". For other cancers, such as alveolar soft part sarcoma and synovial sarcoma, it is considered as a distinctive defining element of the neoplasm (Fletcher CD, 2014; Swerdlow SH et al., 2016). Since fusion genes are diagnostic markers, they can also be used as markers for monitoring minimal residual disease following treatment (De Braekeleer E et al., 2014 ; Hokland P, Ommen HB and Hokland P, 2011). Currently, this strategy is in clinical use mainly for haematological disorders but the improvements in the detection and enrichment of circulating cancer cells and DNA suggest that solid tumors with gene fusions might also be monitored in a similar way (Crowley E et al., 2013; Karabacak NM et al., 2014; Watanabe M et al., 2014; Yu KH et al., 2014; Baccelli I et al., 2013). It is important to mention that the detection of the fusion gene can be used to monitor the progression or the relapse of the cancerous cells but it doesn't need to be an important actor in the neoplastic phenomenon, as long as they are representative and specific of the neoplastic cells (Leary RJ et al., 2010).
Research on fusion genes paved the way to develop specific drugs targeting chimeric proteins. The tyrosine kinase inhibitor Imatinib, approved in 2001, was the first drug specifically designed to target the chimeric protein BCR/ABL1 in CML (Druker BJ et al., 2001; Druker BJ et al., 2001) by blocking its kinase activity. This drug dramatically improved the lifespan and life quality of patients bearing CML. The immense success of imatinib spurred interest in developing new compounds against the chimeric proteins, all of which are kinase inhibitors. Different tumors have shown to display various fusions involving kinase-encoding genes, such as ALK, BRAF, Fibroblast growth factor receptor 3 (FGFR3), neurotrophic tyrosine kinase receptor type 1 (NTRK1), RET and ROS1 (Yoshihara K et al., 2015; ; Huret JL et al., 2013; Kohno T et al., 2013 ; Shaw AT et al., 2013). These fusion genes are occurring at low frequencies but if merged they represent a considerable number of patients. Stratification strategies considering the genotype and phenotype of the tumor would contribute greatly to identifying patients with these very promising treatment targets. Many new compounds are currently being tested in clinical models althought others have reached the Phase 1 and Phase 2 stages in clinical trials, for example, chromatin modifier such as MLL (MEN1 (Malik R et al., 2015), DOT1L (Chen CW et al., 2015), BRD4 (Dawson MA et al., 2011) or EZH2 (McCabe MT et al., 2012; Fillmore CM et al., 2015).
The need for organising data banks
Since discovering their involvement in cancer initiation, progression and evolvement, chromosomal rearrangements have triggered wide, increasing interest to understanding them better. The amount of genes involved has increased, the network underlying certain genes has been resolved and the mechanistic aspect is unravelled. Unfortunately, a lot of work has to be done before cancer has been eradicated. One of the steps is to synthesise all the information and make it available in order to increase the common knowledge of genes that are implicated and their interactions with other pathways in the cell. The importance of creating data banks and reporting various chromosomal rearrangements has been recogniced since the 80's.
1981: Human Genome Mapping
The information on chromosome modification in cancer has been included as part of the Human Genome Mapping (HGM) workshop since 1981. The provision of up-to-date information of all chromosomal rearrangements was the initial goal. This means including all case reports, which are suspected to be the starting point of tumor development or a contribution to the proliferation but also complex karyotypes with several cytogenetic anomalies or secondary modifications leading to the evolution and resistance to treatment.
The increasing number of cases, reports and the multitude of cytogenetically abnormal neoplasms made it too challenging to include everything in the database. In 1991, the HGM decided to focus only on aberrations repeatedly found as sole anomalies in a few given tumor types. As a consequence the number of recurrent changes was severely underestimated, especially in solid tumors where single anomalies are a rare finding. This illustration of chromosomal anomalies mainly represents the tip of the iceberg since the generalisation and improvements in classic cytogenetic techniques and the development of new techniques have considerably increased the number of reports of chromosomal rearrangements in different types of tumors. Several of these anomalies may be of diagnostic and prognostic importance, as well as a large amount of details of molecular analysis.
1983: Catalog of Chromosome Aberrations in Cancer
In 1983, Felix Mitelman published a colossal manuscript that was a supplement to Cytogenetics and Cell Genetics. The goal of this publication was to catalogue all known chromosomal rearrangements. The complexity of the data pushed the laboratories and institutes to adopt computerised methods to compile, revise and index the information. Many cytogeneticist, clinicians and cell biologists were in the demand for a systematic, concise and uniform presentation of material. The vast body of literature was making it complicated to evaluate if a chromosomal abnormality had been described before or not. To facilitate this process, Mitelman presented a compilation of 3,844 published and unpublished cases from colleagues or from his own laboratory. The two volumes presented all the implicated genes, chromosomes and rearrangements known. This set of two books was the first of its kind but far from the last. For several years these two volumes accompanied the bookshelves of several cytogenetists and oncologists. A re-edition of this work took place in 1985 with data of new cases and improved data of cases already described. The number of cases had now increased to a bit more than 5,000. The number of cases increased with each edition so that by the fifth edition it was composed of two large volumes of more than 4,000 pages, making it arduous to use. The sixth edition had already more than 30,000 cases in it. To make it more user friendly it was then published as a CD. The number of cases would still continue to increase and this information was not freely available. Felix Mitelman then had the idea to display the information on the Internet, rendering it freely available. In 2000, the catalogue became accessible for the public under the name Mitelman Database of Chromosome Aberrations in Cancer associated to the Cancer Genome Anatomy Project internet site and under the supervision of the National Cancer Institute (see below).
1997: Atlas of Genetics and Cytogenetics in Oncology and Haematology
How did the idea of the Atlas come about? Prognosis for leukaemia depends on the genes involved: 5 years survival rate: 6% in the inv(3)(q21q26) RPN1/MECOM leukemia, 100% in the dic(9;12)(p13;p13) PAX5/ETV6 leukemia. Treatment depends on the severity of the disease. However, thousands of genes were discovered to be implicated in cancer (14,000 unique fusion transcripts have been detected), and 1,200 types of solid tumors exist. Some cancers are frequent while many others are very rare (many with only 1 published case). This is particularly true for leukemia subtypes of which there are more than 1,000! 25,000 new publications concerning human cancer genetics are added each year to PubMed. No-one has the whole required knowledge, necessary to guide the treatment procedure in case of a rare disease. The following conclusion was made that huge databases were required to collect and summarize data on these rare diseases in order to produce meta-analyses. The Atlas has been established for that reason; to contribute to 'meta-medicine', meaning the mediation between the knowledge and the knowledge users in medicine.
Besides resources dedicated only to cytogenetics, a quick overview of resources in surrounding areas "Cancer Cytogenetics", stricto sensu, deals with chromosomes and cancer. "Cytogenetics" means "Cell Genetics" ("cyto" comes from κ υ τ ο ς, in the meaning of the term "the cell"); "Cytogenomics", as coined by Alain Bernheim, (Bernheim A et al., 2004) (from a princeps paper in French in 1998), means the "genetics -as a whole- of the cell", with complex interconnections and interactions between these operators. As is known for long, "one-gene-one-reaction" (Beadle GW, 1945) (understood today as "one-gene-one-protein"), and we can infer from "Cyto-genomics" to the terms "Cyto-transcriptome" and "Cyto-proteomics", or, in a more holistic approach, (and more simply) "Cell Biology".
Cancer is now known as being a multi-step process, with genetic events at almost each step. Therefore, the "Cancer Cytogenetics" research field should incorporate knowledge of the "Cell Biology" of normal and cancerous cells, gene fusions, mutations or copy number variation, epigenetics, protein domains, metabolic or signaling pathways, as well as consequences of these cytogenomic rearrangements and disorders in the pathogenesis of cancer, from gross and microscopic pathological presentation to patients and diseases, clinical pictures, and, even, to epidemiological data given by cancer registries.
It is useful for the cancer cytogeneticists to have an easy and quick access to databases and books of these surrounding subject areas. Therefore, besides resources of cancer cytogenetics, we will mention other resources, including resources on proteins and resources on cancer.
Presently, Internet provides access to a vast and complex network of knowledge that can make it challenging for you to find the answer to your questions. Several databases are freely accessible, but unfortunately not all of them are user friendly. We will briefly describe the main resources in the following pages.
Recent reviews on cancer databases
In complement, and not to duplicate good recent publications in the last months, some reviews on cancer databases list most of the Internet resources in the general field of cancer genomics. A review of L. Chin gives an overview of the current state if cancer genomics (L. Chin et al., 2011). Regardless of a wide spectrum of references, the topic of cytogenetic resources is absent (Pavlopoulou A et al., 2015 ; Klonowska K et al., 2016 ; Brookes AJ, Robinson PN and Brookes AJ, 2015 ; Yang Y et al., 2015 ; Niroula A and Vihinen M, 2016 ; Diehl AG and Boyle AP, 2016; Martincorena I, et al. 2015). There are also many descriptions of database (and particularly in cancer) in all special issues of Nucleic Acid Reseach (each year in January).
2. GENERAL RESOURCES
Note: a detailed description of General resources in Genetics and/or Oncology may be found at href=http://atlasgeneticsoncology.org/Deep/General_ResourcesID20144.html
PubMed (http://www.ncbi.nlm.nih.gov/pubmed/) is a widely used and free search engine and database of biomedical citations and abstracts, based essentially on the MEDLINE database of references on life sciences and biomedical topics. Medline is the U.S. National Library of Medicine (NLM) premier bibliographic database. PubMed Central (http://www.ncbi.nlm.nih.gov/pmc/) is an archive of biomedical and life sciences journal literature. Articles are deposited by participating journals, as well as for author manuscripts that have been submitted in compliance with the public access policies of participating research funding agencies. Scopus (http://www.scopus.com/) is a database owned by Elsevier.
Gene Nomenclature: The HUGO Gene Nomenclature Committee (HGNC, http://www.genenames.org/) is the authority that assigns standardised nomenclature to human genes. Nomenclature for the description of sequence variations (http://www.hgvs.org/mutnomen/) is maintained by the Human Genome Variation Society (HGVS). International System for Human Cytogenetic Nomenclature (ISCN): The ISCN is the language used to describe abnormal karyotypes. International Classification of Diseases for Oncology, 3rd Edition (ICD-O-3): The WHO/OMS has established a code, which provides a topographical (organ) identifier and an identifier for the detailed pathology.
III- Nucleic acid, genes and protein databases
Nucleic acid databases: GenBank (http://www.ncbi.nlm.nih.gov/genbank/) is a DNA sequence database. The need to have (in parallel to the genome projects) the best representation of genomic and transcript sequences (for diverse species) has been at the origin of consensus databases (as RefSeq, UCSC, Ensembl) with several methods of optimisation. Genomic sequences and transcripts: RefSeq (http://www.ncbi.nlm.nih.gov/refseq/) maintains and curates a database of annotated genomic, transcript, and protein sequence records. Ensembl (http://www.ensembl.org/) developed a software which produces and maintains automatic annotation on selected eukaryotic genomes. The UCSC Genome Browser database (see above) is a large collection containing genome assemblies of various species. Proteins: In addition to the amino acid sequence, protein name and description with domains, these databases may provide a brief annotation information, others are only computationally analysed. These databases are the following: UniProt (http://www.uniprot.org/), a hub consisting of two sections: "TrEMBL" and "Swiss-Prot"; neXtProt (http://www.nextprot.org/db/); PhosphoSitePlus (http://www.phosphosite.org/homeAction.action), an excellent resource providing comprehensive information and tools for the study of protein post-translational modifications; PROSITE (http://prosite.expasy.org/) Pfam (http://pfam.xfam.org/) and InterPro (http://www.ebi.ac.uk/interpro/). The Atlas of Genetics and Cytogenetics in Oncology and Haematology presents highly curated paragraphs with the description of the protein, but on a restricted sample.
Entrez Gene (http://www.ncbi.nlm.nih.gov/gene/) is NCBI's primary text search and retrieval system that integrates the PubMed database and molecular databases including DNA and protein sequence, structure, gene, genome, genetic variation and gene expression. Genecards (http://www.genecards.org/) is a database that provides information on all annotated and predicted human genes.
V- Genome cartography
The cartography of genes on a genome has always been a fundamental mean of representation of genomic information. With the human Genome Project, several types of viewers have been developed. To date, two sites are of first interest for human genetics: The UCSC Genome Browser website (http://genome.ucsc.edu/) contains the reference sequence for a large collection of genomes. The Genome Browser zooms and scrolls over chromosomes, "Blat" quickly maps a sequence to the genome. The UCSC Cancer Browser https://genome-cancer.ucsc.edu/proj/site/help/) allows researchers to interactively explore cancer genomics data and its associated clinical information. Ensembl (http://www.ensembl.org) generates genomic datasets and distributes created datasets and promote standards and interoperability between genomic resources.
VI- Structural variation databases
Genomic structural variation (including insertions, deletions, inversions, translocations and locus copy number changes) accounts for individual differences at the DNA sequence level in humans and can play a major role in diseases. Several databases have integrated data produced in the literature on copy number variation of DNA sequences: dbVar (http://www.ncbi.nlm.nih.gov/dbvar/), DGV - Genomic Variants (http://dgv.tcag.ca/dgv/app/home), DECIPHER (https://decipher.sanger.ac.uk/) and 1000 Genomes (http://www.1000genomes.org/).
VII- Polymorphism databases
It is important to distinguish polymorphisms due to single nucleotide (SNP) as the variability within a population and mutations acquired in a neoplastic process. The determination of variants was previously obtained by SNP arrays, but is nowadays performed by massive parallel sequencing. Polymorphism databases are: dbSNP (http://www.ncbi.nlm.nih.gov/SNP/overview.html), HAPMAP (http://hapmap.ncbi.nlm.nih.gov/index.html.en), 1000 Genomes Project (http://www.1000genomes.org/) and Exome Variant server (EVS) (http://evs.gs.washington.edu/EVS/).
VIII- Portals/Working consortiums
The primary goals of these projects are to generate catalogues of genomic abnormalities (somatic mutations, SNP genotyping, copy number variation profiling, abnormal expression of genes, epigenetic modifications) of series of genes in tumors from different cancer types. The main portals are: TCGA (http://cancergenome.nih.gov/), ICGC: (https://icgc.org/), OASIS (http://www.oasis-genomics.org/) and Firebrowse (http://firebrowse.org/).
IX- Impact on diseases
"Online Mendelian Inheritance in Man" (OMIM, http://omim.org/) is a catalog of human genes and genetic disorders; other databases providing information about human disorders and other phenotypes having a genetic component ClinVar (http://www.ncbi.nlm.nih.gov/clinvar/intro/), MedGen (http://www.ncbi.nlm.nih.gov/medgen/), dbGaP (http://www.ncbi.nlm.nih.gov/dbgap/), SNPs3D (http://www.snps3d.org/) and GTR (http://www.ncbi.nlm.nih.gov/gtr/).
Authoritative books in pathology includes clinical features, morphologic, immunohistochemical and molecular genetic features and prognosis, with a very large iconography. They are the following: the "Rosai and Ackerman's Surgical Pathology" and the "WHO/IARC Classification of Tumours series" (http://publications.iarc.fr/Book-And-Report-Series/Who-Iarc-Classification-Of-Tumours). The Armed Forces Institute of Pathology (AFIP) publishes series of the "AFIP Atlas of Tumor Pathology". The Atlas of Genetics and Cytogenetics in Oncology and Haematology provides complete description of diseases, but again on a limited sample; on the other hand, articles on genes closely related to these diseases are found, right next, in the Atlas. As a product of collaborative work, the usefulness of the Atlas is dependent on colleague participation in updating and completing it. PathologyOutlines (http://pathologyoutlines.com/) provides iconography. To be also noted, the United States and Canadian Academy of Pathology (USCAP, http://www.uscap.org/). The International Classification of Diseases for Oncology, 3rd Edition (ICD-O-3) gives ICD-O codes for each cancer, with an ICD-O3-TOPO, which provides a topographical (organ) identifier and an ICD-O3-MORPH, which provides the basic and detailed pathology.
XI- Cancer Registries
Cancer registries are organizations seeking to collect, store, analyze, and report data on various cancers for epidemiological purposes. The International Agency for Research on Cancer (IARC, http://www.iarc.fr/) is the specialized cancer agency of the World Health Organization (WHO/OMS). It publishes the "Cancer Incidence in Five Continents" series and GLOBOCAN (http://globocan.iarc.fr/Default.aspx). The International Association of Cancer Registries (IACR, http://www.iacr.com.fr/) has developed classifications (the ICD-O), guidelines for registry practices and standard definitions. quality control, consistency checks and basic analysis of data, making data comparable between registries. The European Network of Cancer Registries (ENCR, http://www.encr.eu/) has the same role in Europe as IACR has worldwide. The National Program of Cancer Registries (NPC, http://www.cdc.gov/cancer/), maintained by the Centers for disease control and prevention (CDC), collects data on cancer occurrence in the USA. The Surveillance, Epidemiology, and End Results (SEER, http://seer.cancer.gov/) is a program of the National Cancer Institute. To be cited as well, the Union for International Cancer Control (UICC, http://www.uicc.org/).
XII- Patient associations and interfaces between science and patients - freely accessible services
Associations of parents and friends of patients: These associations of parents of patients with a rare disease are precious. They give moral support and help, and offer practical guidances and information about social benefits, subsidies and day-to-day life to families affected by illness. They often establish a program of grants for research (e.g. Xeroderma Pigmentosum Society (http://www.xps.org/, Sarcoma Foundation of America (http://www.curesarcoma.org/), Union for International Cancer Control (UICC) (http://www.uicc.org/)). Interfaces between science and patients: These sites provide information for patients, including in formation on diseases, professionals for genetic counselling, laboratories, and laboratory tests: GeneTests (https://www.genetests.org/); NORD (http://rarediseases.org); Orphanet (http://www.orpha.net/).
3. CYTOGENOMICS RESOURCES
Note: a detailed description of Cancer Cytogenomics resources may be found at Cancer Cytogenomics resources
I- Chromosome rearrangements/Hybrid genes
The database of chromosome aberrations in cancer counts a total number of cases amounting to more than 60,000, implicating more than 10,000 gene fusions, culled from the literature and organized into distinct sub-databases: The "Cases Quick Searcher" and the "Cases Full Searcher" contain the data related to chromosomal aberrations in individual cases. The "Molecular Biology Associations Searcher" collects cases according to the gene rearrangements. The "Clinical Associations Searcher" is based on tumor characteristics, related to chromosomal aberrations and/or gene rearrangements. This free access database shows raw data and is reliable.
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
The Atlas (http://atlasgeneticsoncology.org) is a peer reviewed on-line journal encyclopaedia and database with free access on the Internet. It is an integrated structure and comprises the following topics: genes, cytogenetics and clinical entities in cancer, and cancer-prone diseases. The Atlas combines various types of knowledge all on one site: genes, gene rearrangements, cytogenetics, protein domains, function, cell biology, pathways. It also contains clinical genetics, including hereditary diseases which are cancer-prone conditions, and diseases, focusing on cancers, but also listing other medical conditions. The Atlas is mainly composed of structured review articles or "cards" (original monographs written by invited authors), The Atlas contributes to the cytogenetic diagnosis and may guide treatment decision makingI
COSMIC (http://cancer.sanger.ac.uk/cosmic) is a catalog of somatic mutations in cancer. It includes all abnormalities, from single nucleotide variations to chromosome rearrangements / fusion genes.
chimerDB 2.0 http://biome.ewha.ac.kr:8080/FusionGene/ is a database of fusion genes with PubMed references and some information about the structure of chimeric genes. TICdb (http://www.unav.es/genetica/TICdb/) is a database of Translocation breakpoints In Cancer with the fusion sequences at the nucleotide level. ChiTARS (http://chitars.bioinfo.cnio.es/) is a database of chimeric transcripts. TCGA Fusion gene Data Portal (http://184.108.40.206/PanCanFusV2/) presents an analysis across tumor types of the TCGA program. Other resources are OMIM (http://www.omim.org/, Fusion cancer (http://donglab.ecnu.edu.cn/databases/FusionCancer/). "Cancer Cytogenetics: Chromosomal and Molecular Genetic Abberations of Tumor Cells" is a book authored by Sverre Heim and Felix Mitelman.
II- Data for SKY and FISH
Fluorescence in-situ hybridization (FISH) technique enables identification of chromosomal structures to be identified using specific probes. This significantly improves the localisation of breakpoints on chromosomes. FISH technique can also be used on non-dividing cells (interphase nuclei). The Cancer Chromosome Aberration Project (CCAP) has generated a set of BAC clones that have been mapped cytogenetically by FISH and physically by STSs to the human genome. The BAC data is integrated into various databases (http://cgap.nci.nih.gov/Chromosomes/CCAPBACClones), (http://mkweb.bcgsc.ca/bacarray/. All BAC can be located on the UCSC genome browser (http://genome.ucsc.edu). BAC from the fishClones file can be visualized on the chromosomal bands on the Atlas (http://atlasgeneticsoncology.org/Bands/). More recently, several commercial companies have developed more specific catalogs of FISH clones as oligonucleotides probes.
III- Comparative genomic hybridization (CGH) resources
This technique detects disequilibria between a disease sample and a normal sample. Several sites are repositories for these CGH/SNP profiles: GEO, http://www.ncbi.nlm.nih.gov/geo/), Array Express (http://www.ebi.ac.uk/arrayexpress/), Tumorscape (http://www.broadinstitute.org/tcga/home), MetaCGH (http://compbio.med.harvard.edu/metacgh/), CaSNP (http://cistrome.org/CaSNP/), Cell line project (http://cancer.sanger.ac.uk/cell_lines), Cancer Cell Line Encyclopedia (http://www.broadinstitute.org/ccle/home) and ArrayMap (http://www.arraymap.org)
IV- Mutation databases
The determination of variants was previously obtained by SNP arrays, but is nowadays performed by massive parallel sequencing. As a result, a huge quantity of polymorphisms and mutations in tumors, are compared to controls. The landscape of the majority of recurrent mutations is now known and can be used for diagnosis. Even in haematological malignancies, where the chromosome rearrangements have shown to bear a major role, nonetheless, it appears now that some mutations at the nucleotide level can still be very important in determining treatments in relation to patient outcome (e.g. ASXL1, ATM, BCL6, BRAF, KRAS and NRAS, CBL, CCND3, CDKN2A and CDKN2C, CEBPA, CRLF2, ETV6, FLT3, GATA2, ID3, IDH1, IDH2, IKZF1, JAK1, KIT, MYD88, NOTCH1, NPM1, RUNX1, TP53). The main mutation databases are: COSMIC (http://cancer.sanger.ac.uk/cosmic), CENSUS (http://cancer.sanger.ac.uk/census/), HGMD (http://www.hgmd.cf.ac.uk/ac/index.php), LOVD (http://www.lovd.nl/3.0/home), TCGA cBIoPortal (http://www.cbioportal.org/), ICGC Data Portal (https://dcc.icgc.org/), OASIS Portal (see above), IntOGen (http://www.intogen.org), BioMuta v2 (https://hive.biochemistry.gwu.edu/tools/biomuta/), DoCM (http://docm.genome.wustl.edu/), CIViC (https://civic.genome.wustl.edu/#/home), and ExAC (http://exac.broadinstitute.org).
TABLE 1: Internet resources
Resource URL Location PMID Last Update Nomenclature The Human Gene Nomenclature Database (HUGO) http://www.genenames.org/ (Hinxton, UK)
26842383 2016 International Classification of Diseases for Oncology, 3rd Edition (ICD-O-3) http://www.who.int/classifications/icd/adaptations/oncology/en/ (IARC, Lyon, Fr)
- 2016 Human Genome Variation Society http://www.hgvs.org/ (Melbourne, Aus)
- 2016 Cards Atlas of Genetics in Oncology and Haematology http://atlasgeneticoncology.org/ (INIST-CNRS, Nancy, Fr)
23161685 2016 Entrez_Gene (NCBI) "http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=gene" (NCBI, Bethesda, US)
26615191 2016 European Bioinformatic Institute (EBI) https://www.ebi.ac.uk (EBI, Hinxton, UK)
26673705 2016 EnSembl (Sanger - EBI) http://www.ensembl.org/ (Sanger_EBI, Hinxton, UK)
26687719 2016 Gencode http://www.gencodegenes.org/ (Sanger Institute, Hinxton, UK)
22955987 2015 GeneCards: human genes, proteins and diseases http://www.genecards.org/ (Weizmann, Rehovot, Is)
27048349 2016 SOURCE http://source-search.princeton.edu/cgi-bin/source/sourceSearch (Princeton, US)
- 2015 AceView http://www.ncbi.nlm.nih.gov/IEB/Research/Acembly/ (NCBI, Bethesda, US)
16925834 2012 GENATLAS http://www.dsi.univ-paris5.fr/genatlas (Imagine, Paris, Fr)
9835018 2016 WikiGenes http://www.wikigenes.org/ (De)
18728691 - H-invDB http://www.h-invitational.jp/hinv/ahg-db/index.jsp (Tokai University,Ja)
23197657 2015 Cancer Portals Genomic Data Commons https://gdc.nci.nih.gov NCI, Bethesda, US)
2016 ICGC Data Portal https://dcc.icgc.org/ (OICR, Ontario, Ca)
21930502 2015 TCGA cBIoPortal http://www.cbioportal.org/public-portal/ (MSKCC, New_York, US)
26852330 2016 Broad Tumor Portal http://www.tumorportal.org/ (Broad Institute, Boston, US)
24390350 2014 Firebrowse GDAC http://firebrowse.org/ (Broad Institute, Boston, US)
- 2016 GTEx Portal http://www.gtexportal.org/home/ (Broad Institute, Boston, US)
25954001 2016 Integrative Onco Genomics (intOgen) http://www.intogen.org/ (Barcelone, Es)
20111033 2014 OASIS Portal http://www.oasis-genomics.org/ (Pfizer, US)
- 2015 Cancer Browser (UCSC) https://genome-cancer.ucsc.edu/ (San Diego, US)
25392408 2015 canSAR https://cansar.icr.ac.uk/ (ICR, London, UK)
26673713 2016 IHEC Data Portal http://epigenomesportal.ca/ihec/ (Mc Gill, Ca)
- Genomic and Cartography Human Genome Browser (UCSC) http://genome.ucsc.edu/goldenPath (San Diego, US)
26590259 2015 Ensembl Map view (Sanger _EBI) http://www.ensembl.org/ (Sanger_EBI, Hinxton, UK)
26687719 2015 NCBI Map Viewer : Homo_sapiens genome view http://www.ncbi.nlm.nih.gov/mapview/ (NCBI, Bethesda, US)
26615191 2015 CGAP : Bac clones http://cgap.nci.nih.gov/Chromosomes/CCAP_BAC_Clones (NCI, Bethesda, US)
- - Gene, transcription and regulation NIH Genetic Sequence database (GenBank) http://www.ncbi.nlm.nih.gov/Genbank/GenbankOverview.html (NCBI, Bethesda, US)
26615191 2016 Reference Sequence database (RefSeq) http://www.ncbi.nlm.nih.gov/refseq/ (NCBI, Bethesda, US)
26615191 2016 Encyclopedia of DNA Elements (ENCODE) https://www.encodeproject.org/ (NHGRI, US)
26962025 2016 The Consensus CDS Project (CCDS) http://www.ncbi.nlm.nih.gov/projects/CCDS/CcdsBrowse.cgi (UCSC, San Diego, US)
24217909 2016 Unigene (NCBI) http://www.ncbi.nlm.nih.gov/UniGene/ (NCBI, Bethesda, US)
26615191 2016 ASG - Alternative Splicing Gallery (ASG) http://statgen.ncsu.edu/asg/ (NCSU, US)
15292448 2004 Gene Expression Atlas (EBI) http://www.ebi.ac.uk/gxa/The ArrayExpress (EBI, Hinxton, UK)
26481351 2016 Gene Expression Omnibus (NCBI) http://www.ncbi.nlm.nih.gov/geo (NCBI, Bethesda, US)
27008011 2016 Exploration of Expression Compendium (SEEK) http://seek.princeton.edu/ (Princeton, US)
25581801 2015 Multi Experiment Matrix (MEM) http://biit.cs.ut.ee/mem/index.cgi (Tartu, Est)
19961599 2012 BioGPS http://biogps.org/ (Scripps, US)
26578587 2016 Human Epigenome http://www.epigenome.org/ (Sanger, UK)
15550986 http://ihec-epigenomes.org/ http://ihec-epigenomes.org/ (Mc Gill, Ca)
Protein : sequence, function, domain, 3D structure Atlas of Genetics in Oncology and Haematology http://atlasgeneticoncology.org/ (INIST-CNRS, Nancy, Fr)
23161685 2016 UniProt http://www.uniprot.org/ (EBI, Hinxton, UK)
26088053 2016 SwissProt http://www.expasy.ch/sprot/ (SIB, Geneve, Ch)
26088053 2016 Swiss-VAR http://swissvar.expasy.org/ (SIB, Geneva, Ch)
20106818 2016 NextProt http://www.nextprot.org/ (SIB, Geneva, Ch)
25593349 2016 ENZYME http://us.expasy.org/enzyme/ (SIB, Geneve, Ch)
10592255 2016 PhosPhoSitePlus http://www.phosphosite.org/ (Danvers, US)
25514926 2014 Prosite: Protein signature http://www.expasy.ch/prosite/ (SIB, Geneva, Ch)
23161676 2016 Protein families (PFAM) http://pfam.xfam.org/ (Sanger, Hinxton, UK)
26673716 2015 A Conserved Domain Database (CDD) http://www.ncbi.nlm.nih.gov/Structure/cdd/cdd.shtml (NCBI, Bethesda, US)
18984618 2015 Domain mapping of disease mutations (DMDM) http://bioinf.umbc.edu/dmdm/ (Baltimore, US)
20685956 2014 Protein domain (PRODOM) http://prodom.prabi.fr/ (PRABI, Lyon, Fr)
12230033 2015 Protein Data Bank (PDB) http://www.rcsb.org/ (San Diego, US)
25428375 2016 Pictorial database of 3D structures (PDBsum) http://www.ebi.ac.uk/thornton-srv/databases/pdbsum/ (EBI, Hinxton, UK)
15608193 2016 Jena Library of Biological Macromolecules (IMB) http://jenalib.fli-leibniz.de/ (Jena, De)
11752308 2015 Structural Biology Knowledgebase (SBKB) http://sbkb.org/pdbid (Rutgers, US)
21472436 2016 Structural Classification of Proteins (SCOP) http://scop.berkeley.edu/search/?ver=2.05 (Berkeley, US)
24304899 2015 Classification of protein structures (CATH) http://www.cathdb.info/ (UCL, London, UK)
25348408 2013 Human Protein Atlas http://www.proteinatlas.org/ (Upsalla, Su)
21572409 2016 Human Protein Reference Database (HPRD) http://www.hprd.org/ (John Hopkins, Baltimore, US)
22159132 2010 Differentially Expressed Proteins in Human Cancer (dbDEPC) http://dbdepc.biosino.org/ (Shanghai, Cn)
22096234 2011 Protein Interaction databases Database of Interacting Proteins (DIP) http://dip.doe-mbi.ucla.edu/dip/Guide.cgi (UCLA, US)
14681454 2014 Molecular Interaction Database (IntAct) http://www.ebi.ac.uk/intact/index.jsp (EBI, Hinxton, UK)
22121220 2016 Functional coupling (FunCoup) http://funcoup.sbc.su.se/ (KTH, Stockholm, Su)
24185702 2013 Biological General Repository for Interaction Datasets (BioGRID) http://thebiogrid.org/ (Toronto, Ca)
26729913 2016 Ontologies - Pathways Gene Ontology http://www.geneontology.org/ -
25378336 2016 QuickGO http://www.ebi.ac.uk/QuickGO/ (EBI, Hinxton, UK)
19744993 2016 Kegg Kyoto Encyclopedia of Genes and Genomes (KEGG) http://www.genome.jp/kegg/ (Kyoto, Jp)
26476454 2016 BioCarta Pathways http://cgap.nci.nih.gov/Pathways/BioCarta_Pathways (NCI, Bethesda, US)
- Reactome http://www.reactome.org/ "(OICR, ca; New-York, US; EBI, UK)"
26656494 2016 Network Data Exchange (NDEx ) http://www.ndexbio.org/ (University of California, US)
26594663 2016 Atlas of Cancer Signalling Networks global map (ACSN) http://acsn.curie.fr/ (Curie, Paris, Fr)
26192618 2013 WikiPathways http://www.wikipathways.org/index.php/ 22096230 2016 Orthology - Evolution The Hierarchical Catalog of Eukaryotic Orthologs (OrthoDB) http://cegg.unige.ch/orthodb5 (Univ. Geneva, Ch)
25428351 2011 TREEFAM: http://www.treefam.org/ (EBI, Hinxton, uk)
24194607 2013 Homologene (NCBI) http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=homologene (NCBI, Bethesda, US)
26615191 2016 Gene Sorter (UCSC) http://genome.ucsc.edu/goldenPath/help/hgNearHelp.html (UCSC, San Diego, US)
15867434 2016 Ortholog groups with inparalogs (InParanoid) http://inparanoid.sbc.su.se/cgi-bin/index.cgi (Stockholm, Su)
25429972 2013 HOVERGEN http://www.prabi.fr/spip.php?article38 (Prabi: Lyon, Fr)
19534752 2009 Gene fusions - Chromosomal Rearrangments Atlas of Genetics in Oncology and Haematology http://atlasgeneticoncology.org/ (INIST-CNRS, Nancy, Fr)
23161685 2016 Mitelman Database of Chromosome Aberrations in Cancer http://cgap.nci.nih.gov/Chromosomes/Mitelman (NCBI, Bethesda, US)
- 2016 Catalog of somatic mutations in Cancer (COSMIC) http://cancer.sanger.ac.uk/cosmic (Sanger Center, Hinxton, UK)
25355519 2016 Database of Translocation breakpoints In Cancer (TICdb) http://www.unav.es/genetica/TICdb/ (Univ Navarre, Sp)
17257420 2013 ChiTARS http://chitars.bioinfo.cnio.es/ (Barcelone, Es)
25414346 2014 TCGA Fusion gene Data Portal http://220.127.116.11/PanCanFusV2/ (MDACC, Houston, US)
25500544 2014 Fusion Cancer http://donglab.ecnu.edu.cn/databases/FusionCancer/index.html (Beijing, Cn)
26215638 2014 ChimerDB 2.0 http://biome.ewha.ac.kr:8080/FusionGene/ (Ewha Womans University, Kr)
19906715 2010 Database of Chromosomal Rearrangements In Disease (dbCRID) http://c1.accurascience.com/dbCRID/ (Houston, US)
21051346 2010 arrayMap - genomic arrays for copy number profiling in human cancer http://www.arraymap.org/ (UZH-SIB, Zurich, Ch)
25428357 2016 CONAN : Cell lines Project: Copy Number Analysis http://www.sanger.ac.uk/cgi-bin/genetics/CGP/conan/search.cgi (Sanger Center, Hinxton, UK)
- 2016 Polymorphisms : SNP, mutations Single Nucleotide Polymorphism (dbSNP) http://www.ncbi.nlm.nih.gov/SNP/overview.html (NCBI, Bethesda, Us)
26615191 2016 The International HapMap Project http://www.hapmap.org/index.html.en (NCBI, Bethesda, US)
20811451 2011 A Deep Catalog of Human Genetic Variation (1000 Genomes) http://www.1000genomes.org/ (EBI, Hinxton, UK)
26432245 2016 Exome Aggregation Consortium (ExAC) http://exac.broadinstitute.org/ (Broad, US)
26791950 2016 Exome Variant server (EVS) http://evs.gs.washington.edu/ (Washington, US)
22604720 2014 ICGC Data Portal http://dcc.icgc.org/ (OICR, Ontario, Ca)
21930502 2015 TCGA Copy Number Portal http://www.broadinstitute.org/tcga/home (Broad Institute, Boston, US)
20164920 2013 Cancer Gene Census http://cancer.sanger.ac.uk/cancergenome/projects/census/ (Sanger Center, Hinxton, UK)
14993899 2016 Catalog of somatic mutations in Cancer (COSMIC) http://www.sanger.ac.uk/perl/CGP/cosmic (Sanger Center, Hinxton, UK)
25355519 2016 Leiden Open Variation Database (LOVD 3.0) http://www.lovd.nl/3.0/home (Leiden, Ne)
21520333 2016 BioMuta v2 https://hive.biochemistry.gwu.edu/tools/biomuta/ (George Washington Univ, Washington DC, US)
24667251 2014 DoCM Database of curated mutations http://docm.genome.wustl.edu/ (WUSTL, US)
- 2016 CIViC Clinical Interpretations of Variants in Cancer https://civic.genome.wustl.edu/#/home (WUSTL, US)
- 2016 NCG5 http://ncg.kcl.ac.uk/ 26516186 2016 Cancer3D http://www.cancer3d.org/ 25392415 2015 Integrative Onco Genomics (intOgen) http://www.intogen.org (Barcelona, Es)
20111033 2014 Human Gene Mutation Database (HGMD ) (*) http://www.hgmd.cf.ac.uk/ac/ (Institute of Medical Genetics, Cardiff, UK)
24077912 2016 Database of genomic structural variation (dbVar) http://www.ncbi.nlm.nih.gov/dbvar/ (Bethesda, NCBI, US)
26615191 2016 DGV -Genomic Variants http://dgv.tcag.ca/dgv/app/home (Toronto, Ca)
24174537 2015 DECIPHER https://decipher.sanger.ac.uk/ Sanger Centre, Hinxton, UK)
19344873 2016 SNPs3D http://www.snps3d.org/ (UMD, US)
16412461 2006 Human Genome Variant Society http://www.hgvs.org/content/guidelines (Melbourne, Aus)
26931183 2016 Diseases Atlas of Genetics in Oncology and Haematology http://atlasgeneticoncology.org/ (INIST-CNRS, Nancy, Fr)
23161685 2016 Online Mendelian Inheritance in Man (OMIM) http://www.omim.org (John Hopkins, Baltimore, US)
25428349 2016 Human medical genetics (MedGen) http://www.ncbi.nlm.nih.gov/medgen/ (NCBI, Bethesda, US)
26615191 2016 Database of Genotypes and Phenotypes (dbGaP) http://www.ncbi.nlm.nih.gov/gap/ (NCBI, Bethesda, US)
26615191 2016 Human variations and phenotypes (ClinVar) http://www.ncbi.nlm.nih.gov/clinvar/intro (NCBI, Bethesda, US)
27037489 2016 The Genetic Testing Registry (GTR) http://www.ncbi.nlm.nih.gov/gtr/ (NIH, Bethesda, US)
23193275 2016 A medical genetics information resource (GeneTests) https://www.genetests.org/disorders/ (Elmwood Park, New Jersey, US)
18073587 2016 HuGE Navigator https://phgkb.cdc.gov/HuGENavigator/home.do (CDC, Atlanta, US)
- 2016 Database of rare diseases and orphan drugs (ORPHANET) http://www.orpha.net/ (INSERM, Paris, Fr)
12655825 2016 National Organization for Rare Diseases (NORD) http://rarediseases.org US
- 2016 Clinical trial, drugs and therapy BioCentury BCIQ http://www.biocentury.com/ (Redwood City, US)
- 2016 The Drug Gene Interaction Database (DgiDB) http://dgidb.genome.wustl.edu/ (WUSTL, US)
26531824 2016 Comparative Genomics Database (CTD ) http://ctd.mdibl.org/ (NC State Univ, US)
25326323 2016 Pharmacogenomics. Knowledge http://www.pharmgkb.org/ (Stanford, US)
- 2016 Genomics of Drug Sensitivity in Cancer (Wellcome Trust) http://www.cancerrxgene.org/ (Sanger, Hinxton, UK)
23180760 2012 Clinical Trial http://clinicaltrials.gov/ct2/search/browse?brwse=intr_cat_ANeo (NIH, Bethesda, US)
- 2016 Cancer registries International Agency for Research on Cancer http://www.iarc.fr/ (Lyon, Fr)
- 2016 International Association of Cancer Registries http://www.iacr.com.fr/ (Lyon, Fr)
- 2016 European Network of Cancer Registries http://www.encr.eu/ - 2016 National Program of Cancer Registries http://www.cdc.gov/cancer/ US
- 2016 Union for International Cancer Control http://www.uicc.org/ US
- 2016 Bibliography, Data mining COREMINE http://www.coremine.com/medical/#search (Oslo, No)
- 2016 Information Hyperlinked over Proteins (iHOP) http://www.ihop-net.org/UniPub/iHOP/ (MSKCC, New-York, US)
18428678 2016 Gene Interactions in Cancer (ZODIAC) http://www.compgenome.org/ZODIAC (Evanston, US)
25956356 2016 PubMed http://www.ncbi.nlm.nih.gov/pubmed (NIH, Bethesda, UrSs)
26615191 2016 Pubmed Central http://www.ncbi.nlm.nih.gov/pmc (NIH, Bethesda, US)
26615191 2016 PubChem http://pubchem.ncbi.nlm.nih.gov/ (NIH, Bethesda, US)
26615191 2016 GoPubMed http://www.gopubmed.org/web/gopubmed/ (NIH, Bethesda, US)
© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Thu Jun 9 10:26:41 MEST 2016
We have briefly discussed the various databases useful for clinicians, students, and researchers in finding answers to their questions and in determining which field in cancer research still needs to be studied. Only a handful of databases or portals take the cytogenetic information into consideration although being one of the first observation points confirming that the cell has transformed into a cancerous cell. Over the years (1960-2016), chimeric genes and fusion proteins have been discovered mainly by cytogenetic means. This has led to understanding of major cancerogenetic processes, and, later on, to the concept of treatments targets for many cases. Cytogenetics, or rather, cytogenomics of cancer, is a major contributor for the concept of "personalized medicine for cancer", together with other tools for other mechanisms. Dorothy Warburton wrote her colleagues in the American Cytogenetics Forum List: Subject: Is Cytogenetics Dying? "I have been told by my department chairman and other advisers that cytogenetics is dying at least three times: in 1968 (just before banding), in 1984 (just before FISH) and in 2001 (just before microarrays) (...) Chromosome changes are being recognised as the cause of more and more abnormalities, not fewer. This is true for both cancer and constitutional cytogenetics (...) There are also a great many basic facts about how chromosome abnormalities originate that we know little about and that are great fields for research".
Besides what is known, there is still a lot to learn about how a mutation or a chromosomal rearrangement is influencing the cellular mechanism.
A decade ago, conventional wisdom was that the expressed genes were regulating all the processes in the cell and the rest of the genome was considered as "junk DNA". The main purpose of this junk DNA was to act as a buffer and to protect the coding part from any kind of aggression. Progressively, we realized that the mutations happening outside the coding regions could influence the expression of nearby genes or in some cases several kilobases away. These mutations were located in regulatory regions recruiting or blocking transcription factors binding DNA.
More elements were found in the "junk DNA" with the discovery of the microRNAs (miRNA) and long non-coding RNAs (lincRNA). Both proved influential in regulating the genome and the expression of several genes. These miRNA and lincRNA are deregulated during the carcinogenic process and studies have demonstrated that by re-establishing the normal expression of one or few miRNAs or lincRNAs, the cancer cells transform back into normal cells. Afterwards, it was observed that genes which were not mutated could be silenced and vice versa. This was due to the epigenetic regulation of the genes and the recruitment of epigenetic regulators in different regions of the genome. The cancerous cells actively modify their own epigenetic marks on the genome to increase the expression of stemness genes providing them with proliferative or resistance advantages.
The chromosome structure in the nucleus is dependent on many variables modulating the chromatin interactions across the whole genome. Techniques like chromatin conformation capture and interphase fluorescent in situ hybridization (FISH) detect spatial associations between specific genes. In the future, they are likely to be the techniques for detecting abnormalities associated with progression of tumours. Similarly, when modifying the 3D structure of chromosomes, it has been demonstrated that the disruption of chromosome neighbourhoods via mutations in insulated neighbourhood boundaries (cohesin CTCF interactions) activates proto-oncogenes in cancer cells (Hnisz D et al., 2016).
As mentioned above, the last build of the human genome (GRCh38, Dec 2013) is more precise than the previous ones and takes into account more haplotypes shared by parts of the human population. Nevertheless, due to a great part of repeated sequences of various classes (50% of the genome), there are some gene families only present at low frequencies, e.g. the insertions of endogenous retroviruses, which represent 8% of the genome and are mostly not localized on GRCh38 for a great part (Wildschutte JH et al., 2016). We need to recognize that such a diversity may be a factor leading to susceptibility to cancer or other diseases.
There is an increasing realisation that our environment, our nutrition and our way of life have an impact on how our cells mutate and how theses mutations are repaired or how the abnormal cells are eliminated by our organism.
It is difficult to fully understand and appreciate the complexity of the cellular mechanism and the various levels that can be deregulated in cancer makes. The use of databases makes this process easier as it condenses the complex information and provides links to other relevant databases providing even more specialized information.
Sequencing of thousands of genomes of patients bearing different types of tumours and genomes of normal persons, generates a huge amount of data demonstrating the complexity of tumours. Focus points are the sensitive parts of the genome which are more prone to be mutated, the expression profiles, the function of the proteins, the pathways the proteins are located in, and the protein interactions (in normal cases and abnormal cases). The same is done at the single cell level, bringing a huge amount of data demonstrating the heterogeneity of the tumour and the interaction with the niche. In principle, this wealth of integrated genomic data and clinical information could reveal the genetic bases of cancer, inherited diseases, and drug responses-illnesses and remedies that have touched nearly every person and family across the globe. This will constitute the databases of tomorrow.
Interpreting these data requires a larger evidence base than any one party alone can develop. However, existing technologies, regulations and approaches are currently not designed for sharing and interpreting this wealth of information effectively, especially across diseases and nations. Databases will need to integrate information increasingly in the upcoming years but also stay interoperable with other databases. This corroborates the idea of having a common nomenclature and language to avoid mistakes but also have common and reliable information (http://www.aacr.org/Research/Research/Pages/aacr-project-genie.aspx#.Vx_mi8f90qx; https://genomicsandhealth.org) in the same manner in which the Working Group for Planetary System Nomenclature maintains the "astronomical naming conventions and planetary nomenclature", any scientific field, confronted with the exponential growth of data, has to create a system of classification and thesaurus for naming of new items, and nosological definitions. This often implies the use of a structured grammar and census of accepted terms/objects.
Resources such as the International System for Human Cytogenetic Nomenclature (ISCN), the International Classification of Diseases for Oncology (ICD-O), the Human Gene Nomenclature Database (HGNC), and the Nomenclature for the description of sequence variations (from the HGVS) are indispensable research tools allowing a common language.
Interoperability: In the context of interoperability between recent cancer projects, such as TCGA and ICGC as well as all data produced by thousands laboratories or hospitals, the Global Alliance for Genomics and Health (Global Alliance, https://genomicsandhealth.org/) (Lawler M et al., 2015) was created to accelerate the potential of genomic medicine. This association brings together over 375 leading institutions working together to generate a common framework of harmonized approaches in enabling the data sharing. In particular, it works to establish interoperable technical standards (standardised language and tools) to management of genomic and clinical data and for a better representation of genotype-phenotype associations.
Open data (open source, open hardware, open content, and open access) is a concept so dear to many, in particular in the medical and scientific world. This concept has recently had a renewed vigour with/since the advent of the Internet. Maintaining the data open and free remains a daily struggle. Everything has a cost, even a free database, from upkeeping and updating the database to providing for the scientific staff necessary to produce expertized data.
Data should remain freely available. However, a business model remains to be established. Although economic investment by the public sector would benefit the whole of mankind, as well as economically profitable in the end, most of the institutional stakeholders are gradually disengaging, and well-known databases are forced to beg for funds (see recent examples, useless to cite them!) or to disappear. This would be a regrettable drawback for the scientific and medical community - yet it may still happen.
Bibliography The cancer genome Stratton MR, Campbell PJ, Futreal PA Nature 2009 Apr 9;458(7239):719-24 PMID 19360079 The emerging complexity of gene fusions in cancer Mertens F, Johansson B, Fioretos T, Mitelman F Nat Rev Cancer 2015 Jun;15(6):371-81 PMID 25998716 Zur Frage der Enstehung maligner Tumoren Boveri T. 1914 Gustav Fischer A minute Chromosome in Human Chronic Ganulocytic Leukemia Nowell PC, Hungerford DA Science 1960 132:1497 Fluorescent labeling of chromosomal DNA: superiority of quinacrine mustard to quinacrine Caspersson T, Zech L, Modest EJ Science 1970 Nov 13;170(3959):762 PMID 5479635 Identificaton of a translocation with quinacrine fluorescence in a patient with acute leukemia Rowley JD Ann Genet 1973 Jun;16(2):109-12 PMID 4125056 A cellular oncogene is translocated to the Philadelphia chromosome in chronic myelocytic leukaemia de Klein A, van Kessel AG, Grosveld G, Bartram CR, Hagemeijer A, Bootsma D, Spurr NK, Heisterkamp N, Groffen J, Stephenson JR Nature 1982 Dec 23;300(5894):765-7 PMID 6960256 Letter: A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining Rowley JD Nature 1973 Jun 1;243(5405):290-3 PMID 4126434 Characteristic chromosomal abnormalities in biopsies and lymphoid-cell lines from patients with Burkitt and non-Burkitt lymphomas Zech L, Haglund U, Nilsson K, Klein G Int J Cancer 1976 Jan 15;17(1):47-56 PMID 946170 A new translocation in Burkitt's tumor cells Berger R, Bernheim A, Weh HJ, Flandrin G, Daniel MT, Brouet JC, Colbert N Hum Genet 1979;53(1):111-2 PMID 535896 2/8 translocation in a Japanese Burkitt's lymphoma Miyoshi I, Hiraki S, Kimura I, Miyamoto K, Sato J Experientia 1979 Jun 15;35(6):742-3 PMID 467575 Variant translocation in Burkitt lymphoma Van Den Berghe H, Gosseye CP, Englebienne V, Cornu G, Sokal G Cancer Genetics and Cytogenetics 1960, 1; 9-14 Chromosomes and causation of human cancer and leukemia Oshimura M, Freeman AI, Sandberg AA XXVI Binding studies in acute lymphoblastic leukemia (ALL) PMID 268996 15/17 translocation, a consistent chromosomal change in acute promyelocytic leukaemia Rowley JD, Golomb HM, Dougherty C Lancet 1977 Mar 5;1(8010):549-50 PMID 65649 Chromosome abnormalities in poorly differentiated lymphocytic lymphoma Fukuhara S, Rowley JD, Variakojis D, Golomb HM Cancer Res 1979 Aug;39(8):3119-28 PMID 582296 Nonrandom chromosome changes involving the Ig gene-carrying chromosomes 12 and 6 in pristane-induced mouse plasmacytomas Ohno S, Babonits M, Wiener F, Spira J, Klein G, Potter M Cell 1979 Dec;18(4):1001-7 PMID 519762 Alveolar rhabdomyosarcoma: a cytogenetic and correlated cytological and histological study Seidal T, Mark J, Hagmar B, Angervall L Acta Pathol Microbiol Immunol Scand A 1982 Sep;90(5):345-54 PMID 7148452 [Translocation of chromosome 22 in Ewing's sarcoma] Aurias A, Rimbaut C, Buffe D, Dubousset J, Mazabraud A C R Seances Acad Sci III 1983;296(23):1105-7 PMID 6416623 [Chromosomal translocation (11; 22) in cell lines of Ewing's sarcoma] Turc-Carel C, Philip I, Berger MP, Philip T, Lenoir G C R Seances Acad Sci III 1983;296(23):1101-3 PMID 6416622 Cytogenetics of a renal adenocarcinoma in a 2-year-old child de Jong B, Molenaar IM, Leeuw JA, Idenberg VJ, Oosterhuis JW Cancer Genet Cytogenet 1986 Mar 15;21(2):165-9 PMID 3004698 6q- and loss of the Y chromosome--two common deviations in malignant human salivary gland tumors Stenman G, Sandros J, Dahlenfors R, Juberg-Ode M, Mark J Cancer Genet Cytogenet 1986 Aug;22(4):283-93 PMID 3015376 The mixed salivary gland tumor Ñ A normally benign human neoplasm frequently showing specific chromosomal abnormalities. Mark J, Dahlenfors R, Ekedahl C, Stenman G Cancer Genetics and Cytogenetics 1980 2, 231-24 Reciprocal translocation t(3;12)(q27;q13) in lipoma Heim S, Mandahl N, Kristoffersson U, Mitelman F, Rser B, Rydholm A, Willén H Cancer Genet Cytogenet 1986 Dec;23(4):301-4 PMID 3779626 Cytogenetic studies of adipose tissue tumors Turc-Carel C, Dal Cin P, Rao U, Karakousis C, Sandberg AA I A benign lipoma with reciprocal translocation t(3;12)(q28;q14) PMID 3779624 Two site-specific deletions and t(1;14) translocation restricted to human T-cell acute leukemias disrupt the 5' part of the tal-1 gene Bernard O, Lecointe N, Jonveaux P, Souyri M, Mauchauffé M, Berger R, Larsen CJ, Mathieu-Mahul D Oncogene 1991 Aug;6(8):1477-88 PMID 1886719 In vivo amplification of the PAX3-FKHR and PAX7-FKHR fusion genes in alveolar rhabdomyosarcoma Barr FG, Nauta LE, Davis RJ, Schäfer BW, Nycum LM, Biegel JA Hum Mol Genet 1996 Jan;5(1):15-21 PMID 8789435 Deregulation of the platelet-derived growth factor B-chain gene via fusion with collagen gene COL1A1 in dermatofibrosarcoma protuberans and giant-cell fibroblastoma Simon MP, Pedeutour F, Sirvent N, Grosgeorge J, Minoletti F, Coindre JM, Terrier-Lacombe MJ, Mandahl N, Craver RD, Blin N, Sozzi G, Turc-Carel C, O'Brien KP, Kedra D, Fransson I, Guilbaud C, Dumanski JP Nat Genet 1997 Jan;15(1):95-8 PMID 8988177 Large deletions at the t(9;22) breakpoint are common and may identify a poor-prognosis subgroup of patients with chronic myeloid leukemia Sinclair PB, Nacheva EP, Leversha M, Telford N, Chang J, Reid A, Bench A, Champion K, Huntly B, Green AR Blood 2000 Feb 1;95(3):738-43 PMID 10648381 FUS-CREB3L2/L1-positive sarcomas show a specific gene expression profile with upregulation of CD24 and FOXL1 Möller E, Hornick JL, Magnusson L, Veerla S, Domanski HA, Mertens F Clin Cancer Res 2011 May 1;17(9):2646-56 PMID 21536545 Genome profiling of chronic myelomonocytic leukemia: frequent alterations of RAS and RUNX1 genes Gelsi-Boyer V, Trouplin V, Adélaïde J, Aceto N, Remy V, Pinson S, Houdayer C, Arnoulet C, Sainty D, Bentires-Alj M, Olschwang S, Vey N, Mozziconacci MJ, Birnbaum D, Chaffanet M BMC Cancer 2008 Oct 16;8:299 PMID 18925961 The recurrent SET-NUP214 fusion as a new HOXA activation mechanism in pediatric T-cell acute lymphoblastic leukemia Van Vlierberghe P, van Grotel M, Tchinda J, Lee C, Beverloo HB, van der Spek PJ, Stubbs A, Cools J, Nagata K, Fornerod M, Buijs-Gladdines J, Horstmann M, van Wering ER, Soulier J, Pieters R, Meijerink JP Blood 2008 May 1;111(9):4668-80 PMID 18299449 Rearrangement of CRLF2 in B-progenitor- and Down syndrome-associated acute lymphoblastic leukemia Mullighan CG, Collins-Underwood JR, Phillips LA, Loudin MG, Liu W, Zhang J, Ma J, Coustan-Smith E, Harvey RC, Willman CL, Mikhail FM, Meyer J, Carroll AJ, Williams RT, Cheng J, Heerema NA, Basso G, Pession A, Pui CH, Raimondi SC, Hunger SP, Downing JR, Carroll WL, Rabin KR Nat Genet 2009 Nov;41(11):1243-6 PMID 19838194 Oncogenic activation of FOXR1 by 11q23 intrachromosomal deletion-fusions in neuroblastoma Santo EE, Ebus ME, Koster J, Schulte JH, Lakeman A, van Sluis P, Vermeulen J, Gisselsson D, Øra I, Lindner S, Buckley PG, Stallings RL, Vandesompele J, Eggert A, Caron HN, Versteeg R, Molenaar JJ Oncogene 2012 Mar 22;31(12):1571-81 PMID 21860421 Fusions involving protein kinase C and membrane-associated proteins in benign fibrous histiocytoma Pńaszczyca A, Nilsson J, Magnusson L, Brosjö O, Larsson O, Vult von Steyern F, Domanski HA, Lilljebjörn H, Fioretos T, Tayebwa J, Mandahl N, Nord KH, Mertens F Int J Biochem Cell Biol 2014 Aug;53:475-81 PMID 24721208 FLNA, a new partner gene fused to MLL in a patient with acute myelomonoblastic leukaemia De Braekeleer E, Douet-Guilbert N, Morel F, Le Bris MJ, Meyer C, Marschalek R, Férec C, De Braekeleer M Br J Haematol 2009 Sep;146(6):693-5 PMID 19622092 The MLL recombinome of acute leukemias in 2013 Meyer C, Hofmann J, Burmeister T, Gröger D, Park TS, Emerenciano M, Pombo de Oliveira M, Renneville A, Villarese P, Macintyre E, Cavé H, Clappier E, Mass-Malo K, Zuna J, Trka J, De Braekeleer E, De Braekeleer M, Oh SH, Tsaur G, Fechina L, van der Velden VH, van Dongen JJ, Delabesse E, Binato R, Silva ML, Kustanovich A, Aleinikova O, Harris MH, Lund-Aho T, Juvonen V, Heidenreich O, Vormoor J, Choi WW, Jarosova M, Kolenova A, Bueno C, Menendez P, Wehner S, Eckert C, Talmant P, Tondeur S, Lippert E, Launay E, Henry C, Ballerini P, Lapillone H, Callanan MB, Cayuela JM, Herbaux C, Cazzaniga G, Kakadiya PM, Bohlander S, Ahlmann M, Choi JR, Gameiro P, Lee DS, Krauter J, Cornillet-Lefebvre P, Te Kronnie G, Schäfer BW, Kubetzko S, Alonso CN, zur Stadt U, Sutton R, Venn NC, Izraeli S, Trakhtenbrot L, Madsen HO, Archer P, Hancock J, Cerveira N, Teixeira MR, Lo Nigro L, Möricke A, Stanulla M, Schrappe M, Sedék L, Szczepański T, Zwaan CM, Coenen EA, van den Heuvel-Eibrink MM, Strehl S, Dworzak M, Panzer-Grümayer R, Dingermann T, Klingebiel T, Marschalek R Leukemia 2013 Nov;27(11):2165-76 PMID 23628958 The new cytogenetics: blurring the boundaries with molecular biology Speicher MR, Carter NP Nat Rev Genet 2005 Oct;6(10):782-92 PMID 16145555 Array comparative genomic hybridization and its applications in cancer Pinkel D, Albertson DG Nat Genet 2005 Jun;37 Suppl:S11-7 Genetic diagnosis in malignant hemopathies: from cytogenetics to next-generation sequencing De Braekeleer E, Douet-Guilbert N, De Braekeleer M Expert Rev Mol Diagn 2014 Mar;14(2):127-9 PMID 24437978 Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer Tomlins SA, Rhodes DR, Perner S, Dhanasekaran SM, Mehra R, Sun XW, Varambally S, Cao X, Tchinda J, Kuefer R, Lee C, Montie JE, Shah RB, Pienta KJ, Rubin MA, Chinnaiyan AM Science 2005 Oct 28;310(5748):644-8 PMID 16254181 A landscape effect in tenosynovial giant-cell tumor from activation of CSF1 expression by a translocation in a minority of tumor cells West RB, Rubin BP, Miller MA, Subramanian S, Kaygusuz G, Montgomery K, Zhu S, Marinelli RJ, De Luca A, Downs-Kelly E, Goldblum JR, Corless CL, Brown PO, Gilks CB, Nielsen TO, Huntsman D, van de Rijn M Proc Natl Acad Sci U S A 2006 Jan 17;103(3):690-5 PMID 16407111 Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer Rikova K, Guo A, Zeng Q, Possemato A, Yu J, Haack H, Nardone J, Lee K, Reeves C, Li Y, Hu Y, Tan Z, Stokes M, Sullivan L, Mitchell J, Wetzel R, Macneill J, Ren JM, Yuan J, Bakalarski CE, Villen J, Kornhauser JM, Smith B, Li D, Zhou X, Gygi SP, Gu TL, Polakiewicz RD, Rush J, Comb MJ Cell 2007 Dec 14;131(6):1190-203 PMID 18083107 Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer Soda M, Choi YL, Enomoto M, Takada S, Yamashita Y, Ishikawa S, Fujiwara S, Watanabe H, Kurashina K, Hatanaka H, Bando M, Ohno S, Ishikawa Y, Aburatani H, Niki T, Sohara Y, Sugiyama Y, Mano H Nature 2007 Aug 2;448(7153):561-6 PMID 17625570 Identification of a novel, recurrent HEY1-NCOA2 fusion in mesenchymal chondrosarcoma based on a genome-wide screen of exon-level expression data Wang L, Motoi T, Khanin R, Olshen A, Mertens F, Bridge J, Dal Cin P, Antonescu CR, Singer S, Hameed M, Bovee JV, Hogendoorn PC, Socci N, Ladanyi M Genes Chromosomes Cancer 2012 Feb;51(2):127-39 PMID 22034177 Identification of somatically acquired rearrangements in cancer using genome-wide massively parallel paired-end sequencing Campbell PJ, Stephens PJ, Pleasance ED, O'Meara S, Li H, Santarius T, Stebbings LA, Leroy C, Edkins S, Hardy C, Teague JW, Menzies A, Goodhead I, Turner DJ, Clee CM, Quail MA, Cox A, Brown C, Durbin R, Hurles ME, Edwards PA, Bignell GR, Stratton MR, Futreal PA Nat Genet 2008 Jun;40(6):722-9 PMID 18438408 Transcriptome sequencing to detect gene fusions in cancer Maher CA, Kumar-Sinha C, Cao X, Kalyana-Sundaram S, Han B, Jing X, Sam L, Barrette T, Palanisamy N, Chinnaiyan AM Nature 2009 Mar 5;458(7234):97-101 PMID 19136943 Chimeric transcript discovery by paired-end transcriptome sequencing Maher CA, Palanisamy N, Brenner JC, Cao X, Kalyana-Sundaram S, Luo S, Khrebtukova I, Barrette TR, Grasso C, Yu J, Lonigro RJ, Schroth G, Kumar-Sinha C, Chinnaiyan AM Proc Natl Acad Sci U S A 2009 Jul 28;106(30):12353-8 PMID 19592507 Complex landscapes of somatic rearrangement in human breast cancer genomes Stephens PJ, McBride DJ, Lin ML, Varela I, Pleasance ED, Simpson JT, Stebbings LA, Leroy C, Edkins S, Mudie LJ, Greenman CD, Jia M, Latimer C, Teague JW, Lau KW, Burton J, Quail MA, Swerdlow H, Churcher C, Natrajan R, Sieuwerts AM, Martens JW, Silver DP, Langerød A, Russnes HE, Foekens JA, Reis-Filho JS, van 't Veer L, Richardson AL, Børresen-Dale AL, Campbell PJ, Futreal PA, Stratton MR Nature 2009 Dec 24;462(7276):1005-10 PMID 20033038 Comprehensive molecular characterization of clear cell renal cell carcinoma Cancer Genome Atlas Research Network Nature 2013 Jul 4;499(7456):43-9 PMID 23792563 Comprehensive genomic characterization of squamous cell lung cancers Cancer Genome Atlas Research Network Nature 2012 Sep 27;489(7417):519-25 PMID 22960745 Comprehensive molecular characterization of urothelial bladder carcinoma Cancer Genome Atlas Research Network Nature 2014 Mar 20;507(7492):315-22 PMID 24476821 Integrated genomic characterization of endometrial carcinoma Cancer Genome Atlas Research Network, Kandoth C, Schultz N, Cherniack AD, Akbani R, Liu Y, Shen H, Robertson AG, Pashtan I, Shen R, Benz CC, Yau C, Laird PW, Ding L, Zhang W, Mills GB, Kucherlapati R, Mardis ER, Levine DA Nature 2013 May 2;497(7447):67-73 PMID 23636398 MHC class II transactivator CIITA is a recurrent gene fusion partner in lymphoid cancers Steidl C, Shah SP, Woolcock BW, Rui L, Kawahara M, Farinha P, Johnson NA, Zhao Y, Telenius A, Neriah SB, McPherson A, Meissner B, Okoye UC, Diepstra A, van den Berg A, Sun M, Leung G, Jones SJ, Connors JM, Huntsman DG, Savage KJ, Rimsza LM, Horsman DE, Staudt LM, Steidl U, Marra MA, Gascoyne RD Nature 2011 Mar 17;471(7338):377-81 PMID 21368758 Use of whole-genome sequencing to diagnose a cryptic fusion oncogene Welch JS, Westervelt P, Ding L, Larson DE, Klco JM, Kulkarni S, Wallis J, Chen K, Payton JE, Fulton RS, Veizer J, Schmidt H, Vickery TL, Heath S, Watson MA, Tomasson MH, Link DC, Graubert TA, DiPersio JF, Mardis ER, Ley TJ, Wilson RK JAMA 2011 Apr 20;305(15):1577-84 PMID 21505136 Genetic alterations activating kinase and cytokine receptor signaling in high-risk acute lymphoblastic leukemia Roberts KG, Morin RD, Zhang J, Hirst M, Zhao Y, Su X, Chen SC, Payne-Turner D, Churchman ML, Harvey RC, Chen X, Kasap C, Yan C, Becksfort J, Finney RP, Teachey DT, Maude SL, Tse K, Moore R, Jones S, Mungall K, Birol I, Edmonson MN, Hu Y, Buetow KE, Chen IM, Carroll WL, Wei L, Ma J, Kleppe M, Levine RL, Garcia-Manero G, Larsen E, Shah NP, Devidas M, Reaman G, Smith M, Paugh SW, Evans WE, Grupp SA, Jeha S, Pui CH, Gerhard DS, Downing JR, Willman CL, Loh M, Hunger SP, Marra MA, Mullighan CG Cancer Cell 2012 Aug 14;22(2):153-66 PMID 22897847 The landscape and therapeutic relevance of cancer-associated transcript fusions Yoshihara K, Wang Q, Torres-Garcia W, Zheng S, Vegesna R, Kim H, Verhaak RG Oncogene 2015 Sep 10;34(37):4845-54 PMID 25500544 Mitelman database of chromosome aberrations and genes fusions in Cancer Mitelman F, Johansson B, Merten sF Mitelman F, Johansson B and Mertens F (Eds.) 2016, http://cgap.nci.nih.gov/Chromosomes/Mitelman Atlas of genetics and cytogenetics in oncology and haematology in 2013 Huret JL, Ahmad M, Arsaban M, Bernheim A, Cigna J, Desangles F, Guignard JC, Jacquemot-Perbal MC, Labarussias M, Leberre V, Malo A, Morel-Pair C, Mossafa H, Potier JC, Texier G, Viguié F, Yau Chun Wan-Senon S, Zasadzinski A, Dessen P Nucleic Acids Res 2013 Jan;41(Database issue):D920-4 PMID 23161685 The impact of translocations and gene fusions on cancer causation Mitelman F, Johansson B, Mertens F Nat Rev Cancer 2007 Apr;7(4):233-45 PMID 17361217 Gene fusions associated with recurrent amplicons represent a class of passenger aberrations in breast cancer Kalyana-Sundaram S, Shankar S, Deroo S, Iyer MK, Palanisamy N, Chinnaiyan AM, Kumar-Sinha C Neoplasia 2012 Aug;14(8):702-8 PMID 22952423 Implications of chimaeric non-co-linear transcripts Gingeras TR Nature 2009 Sep 10;461(7261):206-11 PMID 19741701 SLC45A3-ELK4 is a novel and frequent erythroblast transformation-specific fusion transcript in prostate cancer Rickman DS, Pflueger D, Moss B, VanDoren VE, Chen CX, de la Taille A, Kuefer R, Tewari AK, Setlur SR, Demichelis F, Rubin MA Cancer Res 2009 Apr 1;69(7):2734-8 PMID 19293179 New insights to the MLL recombinome of acute leukemias Meyer C, Kowarz E, Hofmann J, Renneville A, Zuna J, Trka J, Ben Abdelali R, Macintyre E, De Braekeleer E, De Braekeleer M, Delabesse E, de Oliveira MP, Cavé H, Clappier E, van Dongen JJ, Balgobind BV, van den Heuvel-Eibrink MM, Beverloo HB, Panzer-Grümayer R, Teigler-Schlegel A, Harbott J, Kjeldsen E, Schnittger S, Koehl U, Gruhn B, Heidenreich O, Chan LC, Yip SF, Krzywinski M, Eckert C, Möricke A, Schrappe M, Alonso CN, Schäfer BW, Krauter J, Lee DA, Zur Stadt U, Te Kronnie G, Sutton R, Izraeli S, Trakhtenbrot L, Lo Nigro L, Tsaur G, Fechina L, Szczepanski T, Strehl S, Ilencikova D, Molkentin M, Burmeister T, Dingermann T, Klingebiel T, Marschalek R Leukemia 2009 Aug;23(8):1490-9 PMID 19262598 Next-generation sequencing of RNA and DNA isolated from paired fresh-frozen and formalin-fixed paraffin-embedded samples of human cancer and normal tissue Hedegaard J, Thorsen K, Lund MK, Hein AM, Hamilton-Dutoit SJ, Vang S, Nordentoft I, Birkenkamp-Demtröder K, Kruhøffer M, Hager H, Knudsen B, Andersen CL, Sørensen KD, Pedersen JS, Ørntoft TF, Dyrskjøt L PLoS One 2014 May 30;9(5):e98187 PMID 24878701 The evolving classification of soft tissue tumours - an update based on the new 2013 WHO classification Fletcher CD Histopathology 2014 Jan;64(1):2-11 PMID 24164390 The 2016 revision of the World Health Organization (WHO) classification of lymphoid neoplasms Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R, Advani R, Ghielmini M, Salles GA, Zelenetz AD, Jaffe ES Blood 2016 Mar 15 PMID 26980727 Towards individualized follow-up in adult acute myeloid leukemia in remission Hokland P, Ommen HB Blood 2011 Mar 3;117(9):2577-84 PMID 21097673 Liquid biopsy: monitoring cancer-genetics in the blood Crowley E, Di Nicolantonio F, Loupakis F, Bardelli A Nat Rev Clin Oncol 2013 Aug;10(8):472-84 PMID 23836314 Microfluidic, marker-free isolation of circulating tumor cells from blood samples Karabacak NM, Spuhler PS, Fachin F, Lim EJ, Pai V, Ozkumur E, Martel JM, Kojic N, Smith K, Chen PI, Yang J, Hwang H, Morgan B, Trautwein J, Barber TA, Stott SL, Maheswaran S, Kapur R, Haber DA, Toner M Nat Protoc 2014 Mar;9(3):694-710 PMID 24577360 A novel flow cytometry-based cell capture platform for the detection, capture and molecular characterization of rare tumor cells in blood Watanabe M, Serizawa M, Sawada T, Takeda K, Takahashi T, Yamamoto N, Koizumi F, Koh Y J Transl Med 2014 May 23;12:143 PMID 24886394 Pharmacogenomic modeling of circulating tumor and invasive cells for prediction of chemotherapy response and resistance in pancreatic cancer Yu KH, Ricigliano M, Hidalgo M, Abou-Alfa GK, Lowery MA, Saltz LB, Crotty JF, Gary K, Cooper B, Lapidus R, Sadowska M, O'Reilly EM Clin Cancer Res 2014 Oct 15;20(20):5281-9 PMID 25107917 Identification of a population of blood circulating tumor cells from breast cancer patients that initiates metastasis in a xenograft assay Baccelli I, Schneeweiss A, Riethdorf S, Stenzinger A, Schillert A, Vogel V, Klein C, Saini M, Bäuerle T, Wallwiener M, Holland-Letz T, Höfner T, Sprick M, Scharpff M, Marmé F, Sinn HP, Pantel K, Weichert W, Trumpp A Nat Biotechnol 2013 Jun;31(6):539-44 PMID 23609047 Development of personalized tumor biomarkers using massively parallel sequencing Leary RJ, Kinde I, Diehl F, Schmidt K, Clouser C, Duncan C, Antipova A, Lee C, McKernan K, De La Vega FM, Kinzler KW, Vogelstein B, Diaz LA Jr, Velculescu VE Sci Transl Med 2010 Feb 24;2(20):20ra14 PMID 20371490 Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome Druker BJ, Sawyers CL, Kantarjian H, Resta DJ, Reese SF, Ford JM, Capdeville R, Talpaz M N Engl J Med 2001 Apr 5;344(14):1038-42 PMID 11287973 Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia Druker BJ, Talpaz M, Resta DJ, Peng B, Buchdunger E, Ford JM, Lydon NB, Kantarjian H, Capdeville R, Ohno-Jones S, Sawyers CL N Engl J Med 2001 Apr 5;344(14):1031-7 PMID 11287972 Imatinib mesylate in advanced dermatofibrosarcoma protuberans: pooled analysis of two phase II clinical trials Rutkowski P, Van Glabbeke M, Rankin CJ, Ruka W, Rubin BP, Debiec-Rychter M, Lazar A, Gelderblom H, Sciot R, Lopez-Terrada D, Hohenberger P, van Oosterom AT, Schuetze SM; European Organisation for Research and Treatment of Cancer Soft Tissue/Bone Sarcoma Group; Southwest Oncology Group J Clin Oncol 2010 Apr 1;28(10):1772-9 PMID 20194851 Adjuvant treatment of GIST: patient selection and treatment strategies Joensuu H Nat Rev Clin Oncol 2012 Apr 24;9(6):351-8 PMID 22525709 Philadelphia chromosome-positive acute lymphoblastic leukemia: current treatment and future perspectives Lee HJ, Thompson JE, Wang ES, Wetzler M Cancer 2011 Apr 15;117(8):1583-94 PMID 21472706 RET fusion gene: translation to personalized lung cancer therapy Kohno T, Tsuta K, Tsuchihara K, Nakaoku T, Yoh K, Goto K Cancer Sci 2013 Nov;104(11):1396-400 PMID 23991695 Tyrosine kinase gene rearrangements in epithelial malignancies Shaw AT, Hsu PP, Awad MM, Engelman JA Nat Rev Cancer 2013 Nov;13(11):772-87 PMID 24132104 Targeting the MLL complex in castration-resistant prostate cancer Malik R, Khan AP, Asangani IA, Cielik M, Prensner JR, Wang X, Iyer MK, Jiang X, Borkin D, Escara-Wilke J, Stender R, Wu YM, Niknafs YS, Jing X, Qiao Y, Palanisamy N, Kunju LP, Krishnamurthy PM, Yocum AK, Mellacheruvu D, Nesvizhskii AI, Cao X, Dhanasekaran SM, Feng FY, Grembecka J, Cierpicki T, Chinnaiyan AM Nat Med 2015 Apr;21(4):344-52 PMID 25822367 DOT1L inhibits SIRT1-mediated epigenetic silencing to maintain leukemic gene expression in MLL-rearranged leukemia Chen CW, Koche RP, Sinha AU, Deshpande AJ, Zhu N, Eng R, Doench JG, Xu H, Chu SH, Qi J, Wang X, Delaney C, Bernt KM, Root DE, Hahn WC, Bradner JE, Armstrong SA Nat Med 2015 Apr;21(4):335-43 PMID 25822366 Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia Dawson MA, Prinjha RK, Dittmann A, Giotopoulos G, Bantscheff M, Chan WI, Robson SC, Chung CW, Hopf C, Savitski MM, Huthmacher C, Gudgin E, Lugo D, Beinke S, Chapman TD, Roberts EJ, Soden PE, Auger KR, Mirguet O, Doehner K, Delwel R, Burnett AK, Jeffrey P, Drewes G, Lee K, Huntly BJ, Kouzarides T Nature 2011 Oct 2;478(7370):529-33 PMID 21964340 EZH2 inhibition as a therapeutic strategy for lymphoma with EZH2-activating mutations McCabe MT, Ott HM, Ganji G, Korenchuk S, Thompson C, Van Aller GS, Liu Y, Graves AP, Della Pietra A 3rd, Diaz E, LaFrance LV, Mellinger M, Duquenne C, Tian X, Kruger RG, McHugh CF, Brandt M, Miller WH, Dhanak D, Verma SK, Tummino PJ, Creasy CL Nature 2012 Dec 6;492(7427):108-12 PMID 23051747 EZH2 inhibition sensitizes BRG1 and EGFR mutant lung tumours to TopoII inhibitors Fillmore CM, Xu C, Desai PT, Berry JM, Rowbotham SP, Lin YJ, Zhang H, Marquez VE, Hammerman PS, Wong KK, Kim CF Nature 2015 Apr 9;520(7546):239-42 PMID 25629630 [Cytogenetics, cytogenomics and cancer: 2004 update] Bernheim A, Huret JL, Guillaud-Bataille M, Brison O, Couturiers J; Groupe Français de Cytogéné Oncologique Bull Cancer 2004 Jan;91(1):29-43 PMID 14975803 Genetics and metabolism in Neurospora BEADLE GW Physiol Rev 1945 Oct;25:643-63 PMID 21004451 The GenBank nucleic acid sequence database Burks C, Fickett JW, Goad WB, Kanehisa M, Lewitter FI, Rindone WP, Swindell CD, Tung CS, Bilofsky HS Comput Appl Biosci 1985 Dec;1(4):225-33 PMID 3880345 GenBank Burks C, Cassidy M, Cinkosky MJ, Cumella KE, Gilna P, Hayden JE, Keen GM, Kelley TA, Kelly M, Kristofferson D, et al Nucleic Acids Res 1991 Apr 25;19 Suppl:2221-5 PMID 2041806 Recent changes in the GenBank On-line Service Benton D Nucleic Acids Res 1990 Mar 25;18(6):1517-20 PMID 2326192 GenBank Benson DA, Clark K, Karsch-Mizrachi I, Lipman DJ, Ostell J, Sayers EW Nucleic Acids Res 2015 Jan;43(Database issue):D30-5 PMID 25414350 The European Bioinformatics Institute in 2016: Data growth and integration Cook CE, Bergman MT, Finn RD, Cochrane G, Birney E, Apweiler R Nucleic Acids Res 2016 Jan 4;44(D1):D20-6 PMID 26673705 Searching and Navigating UniProt Databases Pundir S, Magrane M, Martin MJ, O'Donovan C; UniProt Consortium Curr Protoc Bioinformatics 2015 Jun 19;50:1 PMID 26088053 Genenames.org Gray KA, Yates B, Seal RL, Wright MW, Bruford EA the HGNC resources in 2015 Nucleic Acids Res PMID 25361968 Database resources of the National Center for Biotechnology Information NCBI Resource Coordinators Nucleic Acids Res 2016 Jan 4;44(D1):D7-19 PMID 26615191 Genic insights from integrated human proteomics in GeneCards Fishilevich S, Zimmerman S, Kohn A, Iny Stein T, Olender T, Kolker E, Safran M, Lancet D Database (Oxford) 2016 Apr 5;2016 PMID 27048349 The UCSC Cancer Genomics Browser: update 2015 Goldman M, Craft B, Swatloski T, Cline M, Morozova O, Diekhans M, Haussler D, Zhu J Nucleic Acids Res 2015 Jan;43(Database issue):D812-7 PMID 25392408 Ensembl 2016 Yates A, Akanni W, Amode MR, Barrell D, Billis K, Carvalho-Silva D, Cummins C, Clapham P, Fitzgerald S, Gil L, Girón CG, Gordon L, Hourlier T, Hunt SE, Janacek SH, Johnson N, Juettemann T, Keenan S, Lavidas I, Martin FJ, Maurel T, McLaren W, Murphy DN, Nag R, Nuhn M, Parker A, Patricio M, Pignatelli M, Rahtz M, Riat HS, Sheppard D, Taylor K, Thormann A, Vullo A, Wilder SP, Zadissa A, Birney E, Harrow J, Muffato M, Perry E, Ruffier M, Spudich G, Trevanion SJ, Cunningham F, Aken BL, Zerbino DR, Flicek P Nucleic Acids Res 2016 Jan 4;44(D1):D710-6 PMID 26687719 Integrated genomic analyses of ovarian carcinoma Cancer Genome Atlas Research Network Nature 2011 Jun 29;474(7353):609-15 PMID 21720365 International Cancer Genome Consortium Data Portal--a one-stop shop for cancer genomics data Zhang J, Baran J, Cros A, Guberman JM, Haider S, Hsu J, Liang Y, Rivkin E, Wang J, Whitty B, Wong-Erasmus M, Yao L, Kasprzyk A Database (Oxford) 2011 Sep 19;2011:bar026 PMID 21930502 Making sense of cancer genomic data. Chin L, Hahn WC, Getz G, Meyerson M. Genes Dev. 2011 Mar 15;25(6):534-55. doi: 10.1101/gad.2017311. PMID 21406553 Human cancer databases (review) Pavlopoulou A, Spandidos DA, Michalopoulos I Oncol Rep 2015 Jan;33(1):3-18 PMID 25369839 Oncogenomic portals for the visualization and analysis of genome-wide cancer data Klonowska K, Czubak K, Wojciechowska M, Handschuh L, Zmienko A, Figlerowicz M, Dams-Kozlowska H, Kozlowski P Oncotarget 2016 Jan 5;7(1):176-92 PMID 26484415 Human genotype-phenotype databases: aims, challenges and opportunities Brookes AJ, Robinson PN Nat Rev Genet 2015 Dec;16(12):702-15 PMID 26553330 Databases and web tools for cancer genomics study Yang Y, Dong X, Xie B, Ding N, Chen J, Li Y, Zhang Q, Qu H, Fang X Genomics Proteomics Bioinformatics 2015 Feb;13(1):46-50 PMID 25707591 Variation Interpretation Predictors: Principles, Types, Performance, and Choice Niroula A, Vihinen M Hum Mutat 2016 Jun;37(6):579-97 PMID 26987456 Deciphering ENCODE Diehl AG, Boyle AP Trends Genet 2016 Apr;32(4):238-49 PMID 26962025 dbWGFP: a database and web server of human whole-genome single nucleotide variants and their functional predictions Wu J, Wu M, Li L, Liu Z, Zeng W, Jiang R Database (Oxford) 2016 Mar 17;2016 PMID 26989155 Somatic mutation in cancer and normal cells Martincorena I, Campbell PJ Science 2015 Sep 25;349(6255):1483-9 PMID 26404825 Cancer Cytogenetics: Chromosomal and Molecular Genetic Abberations of Tumor Cells Sverre Heim and Felix Mitelman 2015, Wiley-Blackwell , New-York A database on cytogenetics in haematology and oncology Dorkeld F, Bernheim A, Dessen P, Huret JL Nucleic Acids Res 1999 Jan 1;27(1):353-4 PMID 9847226 Lancet A PROPOSED standard system of nomenclature of human mitotic chromosomes 1960 May 14;1(7133):1063-5 PubMed PMID: 13857542 PMID 13857542 An International System for Human Cytogenetic Nomenclature Shaffer LG, McGowen-Jordan J, Schmid M, editors 2013, Basel: S. Karger Mitelman database of chromosome aberrations and genes fusions in Cancer Mitelman F, Johansson B, Mertens F ChimerDB--a knowledgebase for fusion sequences Kim N, Kim P, Nam S, Shin S, Lee S Nucleic Acids Res 2006 Jan 1;34(Database issue):D21-4 PMID 16381848 ChimerDB 2 Kim P, Yoon S, Kim N, Lee S, Ko M, Lee H, Kang H, Kim J, Lee S 0--a knowledgebase for fusion genes updated Nucleic Acids Res PMID 19906715 TICdb: a collection of gene-mapped translocation breakpoints in cancer Novo FJ, de Mendíbil IO, Vizmanos JL BMC Genomics 2007 Jan 26;8:33 PMID 17257420 OMIM Amberger JS, Bocchini CA, Schiettecatte F, Scott AF, Hamosh A org: Online Mendelian Inheritance in Man (OMIM), an online catalog of human genes and genetic disorders Nucleic Acids Res PMID 25428349 COSMIC: exploring the world's knowledge of somatic mutations in human cancer Forbes SA, Beare D, Gunasekaran P, Leung K, Bindal N, Boutselakis H, Ding M, Bamford S, Cole C, Ward S, Kok CY, Jia M, De T, Teague JW, Stratton MR, McDermott U, Campbell PJ Nucleic Acids Res 2015 Jan;43(Database issue):D805-11 PMID 25355519 ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data Frenkel-Morgenstern M, Gorohovski A, Lacroix V, Rogers M, Ibanez K, Boullosa C, Andres Leon E, Ben-Hur A, Valencia A Nucleic Acids Res 2013 Jan;41(Database issue):D142-51 PMID 23143107 ChiTaRS 2 Frenkel-Morgenstern M, Gorohovski A, Vucenovic D, Maestre L, Valencia A 1--an improved database of the chimeric transcripts and RNA-seq data with novel sense-antisense chimeric RNA transcripts Nucleic Acids Res PMID 25414346 A comprehensive transcriptional portrait of human cancer cell lines Klijn C, Durinck S, Stawiski EW, Haverty PM, Jiang Z, Liu H, Degenhardt J, Mayba O, Gnad F, Liu J, Pau G, Reeder J, Cao Y, Mukhyala K, Selvaraj SK, Yu M, Zynda GJ, Brauer MJ, Wu TD, Gentleman RC, Manning G, Yauch RL, Bourgon R, Stokoe D, Modrusan Z, Neve RM, de Sauvage FJ, Settleman J, Seshagiri S, Zhang Z Nat Biotechnol 2015 Mar;33(3):306-12 PMID 25485619 FusionCancer: a database of cancer fusion genes derived from RNA-seq data Wang Y, Wu N, Liu J, Wu Z, Dong D Diagn Pathol 2015 Jul 28;10:131 PMID 26215638 Fusion gene microarray reveals cancer type-specificity among fusion genes Løvf M, Thomassen GO, Bakken AC, Celestino R, Fioretos T, Lind GE, Lothe RA, Skotheim RI Genes Chromosomes Cancer 2011 May;50(5):348-57 PMID 21305644 A universal assay for detection of oncogenic fusion transcripts by oligo microarray analysis Skotheim RI, Thomassen GO, Eken M, Lind GE, Micci F, Ribeiro FR, Cerveira N, Teixeira MR, Heim S, Rognes T, Lothe RA Mol Cancer 2009 Jan 19;8:5 PMID 19152679 Next generation sequencing approach for detecting 491 fusion genes from human cancer Urakami K, Shimoda Y, Ohshima K, Nagashima T, Serizawa M, Tanabe T, Saito J, Usui T, Watanabe Y, Naruoka A, Ohnami S, Ohnami S, Mochizuki T, Kusuhara M, Yamaguchi K Biomed Res 2016;37(1):51-62 PMID 26912140 Recurrent chimeric fusion RNAs in non-cancer tissues and cells Babiceanu M, Qin F, Xie Z, Jia Y, Lopez K, Janus N, Facemire L, Kumar S, Pang Y, Qi Y, Lazar IM, Li H Nucleic Acids Res 2016 Apr 7;44(6):2859-72 PMID 26837576 Comparative genomic hybridization for molecular cytogenetic analysis of solid tumors Kallioniemi A, Kallioniemi OP, Sudar D, Rutovitz D, Gray JW, Waldman F, Pinkel D Science 1992 Oct 30;258(5083):818-21 PMID 1359641 Matrix-based comparative genomic hybridization: biochips to screen for genomic imbalances Solinas-Toldo S, Lampel S, Stilgenbauer S, Nickolenko J, Benner A, Döhner H, Cremer T, Lichter P Genes Chromosomes Cancer 1997 Dec;20(4):399-407 PMID 9408757 High resolution analysis of DNA copy number variation using comparative genomic hybridization to microarrays Pinkel D, Segraves R, Sudar D, Clark S, Poole I, Kowbel D, Collins C, Kuo WL, Chen C, Zhai Y, Dairkee SH, Ljung BM, Gray JW, Albertson DG Nat Genet 1998 Oct;20(2):207-11 PMID 9771718 Impact of centralization on aCGH-based genomic profiles for precision medicine in oncology Commo F, Ferté C, Soria JC, Friend SH, André F, Guinney J Ann Oncol 2015 Mar;26(3):582-8 PMID 25538175 The Gene Expression Omnibus Database Clough E, Barrett T Methods Mol Biol 2016;1418:93-110 PMID 27008011 Expression Atlas update--an integrated database of gene and protein expression in humans, animals and plants Petryszak R, Keays M, Tang YA, Fonseca NA, Barrera E, Burdett T, Füllgrabe A, Fuentes AM, Jupp S, Koskinen S, Mannion O, Huerta L, Megy K, Snow C, Williams E, Barzine M, Hastings E, Weisser H, Wright J, Jaiswal P, Huber W, Choudhary J, Parkinson HE, Brazma A Nucleic Acids Res 2016 Jan 4;44(D1):D746-52 PMID 26481351 The landscape of somatic copy-number alteration across human cancers Beroukhim R, Mermel CH, Porter D, Wei G, Raychaudhuri S, Donovan J, Barretina J, Boehm JS, Dobson J, Urashima M, Mc Henry KT, Pinchback RM, Ligon AH, Cho YJ, Haery L, Greulich H, Reich M, Winckler W, Lawrence MS, Weir BA, Tanaka KE, Chiang DY, Bass AJ, Loo A, Hoffman C, Prensner J, Liefeld T, Gao Q, Yecies D, Signoretti S, Maher E, Kaye FJ, Sasaki H, Tepper JE, Fletcher JA, Tabernero J, Baselga J, Tsao MS, Demichelis F, Rubin MA, Janne PA, Daly MJ, Nucera C, Levine RL, Ebert BL, Gabriel S, Rustgi AK, Antonescu CR, Ladanyi M, Letai A, Garraway LA, Loda M, Beer DG, True LD, Okamoto A, Pomeroy SL, Singer S, Golub TR, Lander ES, Getz G, Sellers WR, Meyerson M Nature 2010 Feb 18;463(7283):899-905 PMID 20164920 Functional genomic analysis of chromosomal aberrations in a compendium of 8000 cancer genomes Kim TM, Xi R, Luquette LJ, Park RW, Johnson MD, Park PJ Genome Res 2013 Feb;23(2):217-27 PMID 23132910 CaSNP: a database for interrogating copy number alterations of cancer genome from SNP array data Cao Q, Zhou M, Wang X, Meyer CA, Zhang Y, Chen Z, Li C, Liu XS Nucleic Acids Res 2011 Jan;39(Database issue):D968-74 PMID 20972221 arrayMap 2014: an updated cancer genome resource Cai H, Gupta S, Rath P, Ai N, Baudis M Nucleic Acids Res 2015 Jan;43(Database issue):D825-30 PMID 25428357 Detection of large-scale variation in the human genome Iafrate AJ, Feuk L, Rivera MN, Listewnik ML, Donahoe PK, Qi Y, Scherer SW, Lee C Nat Genet 2004 Sep;36(9):949-51 PMID 15286789 Global variation in copy number in the human genome Redon R, Ishikawa S, Fitch KR, Feuk L, Perry GH, Andrews TD, Fiegler H, Shapero MH, Carson AR, Chen W, Cho EK, Dallaire S, Freeman JL, González JR, Gratacòs M, Huang J, Kalaitzopoulos D, Komura D, MacDonald JR, Marshall CR, Mei R, Montgomery L, Nishimura K, Okamura K, Shen F, Somerville MJ, Tchinda J, Valsesia A, Woodwark C, Yang F, Zhang J, Zerjal T, Zhang J, Armengol L, Conrad DF, Estivill X, Tyler-Smith C, Carter NP, Aburatani H, Lee C, Jones KW, Scherer SW, Hurles ME Nature 2006 Nov 23;444(7118):444-54 PMID 17122850 The Database of Genomic Variants: a curated collection of structural variation in the human genome MacDonald JR, Ziman R, Yuen RK, Feuk L, Scherer SW Nucleic Acids Res 2014 Jan;42(Database issue):D986-92 PMID 24174537 DECIPHER: Database of Chromosomal Imbalance and Phenotype in Humans Using Ensembl Resources Firth HV, Richards SM, Bevan AP, Clayton S, Corpas M, Rajan D, Van Vooren S, Moreau Y, Pettett RM, Carter NP Am J Hum Genet 2009 Apr;84(4):524-33 A global reference for human genetic variation 1000 Genomes Project Consortium, Auton A, Brooks LD, Durbin RM, Garrison EP, Kang HM, Korbel JO, Marchini JL, McCarthy S, McVean GA, Abecasis GR Nature 2015 Oct 1;526(7571):68-74 PMID 26432245 Integrating common and rare genetic variation in diverse human populations International HapMap 3 Consortium, Altshuler DM, Gibbs RA, Peltonen L, Altshuler DM, Gibbs RA, Peltonen L, Dermitzakis E, Schaffner SF, Yu F, Peltonen L, Dermitzakis E, Bonnen PE, Altshuler DM, Gibbs RA, de Bakker PI, Deloukas P, Gabriel SB, Gwilliam R, Hunt S, Inouye M, Jia X, Palotie A, Parkin M, Whittaker P, Yu F, Chang K, Hawes A, Lewis LR, Ren Y, Wheeler D, Gibbs RA, Muzny DM, Barnes C, Darvishi K, Hurles M, Korn JM, Kristiansson K, Lee C, McCarrol SA, Nemesh J, Dermitzakis E, Keinan A, Montgomery SB, Pollack S, Price AL, Soranzo N, Bonnen PE, Gibbs RA, Gonzaga-Jauregui C, Keinan A, Price AL, Yu F, Anttila V, Brodeur W, Daly MJ, Leslie S, McVean G, Moutsianas L, Nguyen H, Schaffner SF, Zhang Q, Ghori MJ, McGinnis R, McLaren W, Pollack S, Price AL, Schaffner SF, Takeuchi F, Grossman SR, Shlyakhter I, Hostetter EB, Sabeti PC, Adebamowo CA, Foster MW, Gordon DR, Licinio J, Manca MC, Marshall PA, Matsuda I, Ngare D, Wang VO, Reddy D, Rotimi CN, Royal CD, Sharp RR, Zeng C, Brooks LD, McEwen JE Nature 2010 Sep 2;467(7311):52-8 PMID 20811451 Evolution and functional impact of rare coding variation from deep sequencing of human exomes Tennessen JA, Bigham AW, O'Connor TD, Fu W, Kenny EE, Gravel S, McGee S, Do R, Liu X, Jun G, Kang HM, Jordan D, Leal SM, Gabriel S, Rieder MJ, Abecasis G, Altshuler D, Nickerson DA, Boerwinkle E, Sunyaev S, Bustamante CD, Bamshad MJ, Akey JM; Broad GO; Seattle GO; NHLBI Exome Sequencing Project Science 2012 Jul 6;337(6090):64-9 PMID 22604720 A census of human cancer genes Futreal PA, Coin L, Marshall M, Down T, Hubbard T, Wooster R, Rahman N, Stratton MR Nat Rev Cancer 2004 Mar;4(3):177-83 PMID 14993899 Human Gene Mutation Database Cooper DN, Krawczak M Hum Genet 1996 Nov;98(5):629 PMID 8882888 LOVD v. 2.0: the next generation in gene variant databases. Fokkema IF, Taschner PE, Schaafsma GC, Celli J, Laros JF, den Dunnen JT Hum Mutat. May;32(5):557-63 PMID 21520333 Web-TCGA: an online platform for integrated analysis of molecular cancer data sets Deng M, Brägelmann J, Schultze JL, Perner S BMC Bioinformatics 2016 Feb 6;17:72 PMID 26852330 IntOGen: integration and data mining of multidimensional oncogenomic data Gundem G, Perez-Llamas C, Jene-Sanz A, Kedzierska A, Islam A, Deu-Pons J, Furney SJ, Lopez-Bigas N Nat Methods 2010 Feb;7(2):92-3 PMID 20111033 A framework for organizing cancer-related variations from existing databases, publications and NGS data using a High-performance Integrated Virtual Environment (HIVE) Wu TJ, Shamsaddini A, Pan Y, Smith K, Crichton DJ, Simonyan V, Mazumder R Database (Oxford) 2014 Mar 25;2014:bau022 PMID 24667251 Quantifying prion disease penetrance using large population control cohorts Minikel EV, Vallabh SM, Lek M, Estrada K, Samocha KE, Sathirapongsasuti JF, McLean CY, Tung JY, Yu LP, Gambetti P, Blevins J, Zhang S, Cohen Y, Chen W, Yamada M, Hamaguchi T, Sanjo N, Mizusawa H, Nakamura Y, Kitamoto T, Collins SJ, Boyd A, Will RG, Knight R, Ponto C, Zerr I, Kraus TF, Eigenbrod S, Giese A, Calero M, de Pedro-Cuesta J, Haïk S, Laplanche JL, Bouaziz-Amar E, Brandel JP, Capellari S, Parchi P, Poleggi A, Ladogana A, O'Donnell-Luria AH, Karczewski KJ, Marshall JL, Boehnke M, Laakso M, Mohlke KL, Kähler A, Chambert K, McCarroll S, Sullivan PF, Hultman CM, Purcell SM, Sklar P, van der Lee SJ, Rozemuller A, Jansen C, Hofman A, Kraaij R, van Rooij JG, Ikram MA, Uitterlinden AG, van Duijn CM; Exome Aggregation Consortium (ExAC), Daly MJ, MacArthur DG Sci Transl Med 2016 Jan 20;8(322):322ra9 PMID 26791950 Birth Defects Cytogenet Cell Genet. 1974;13(3):1-216 Using ClinVar as a Resource to Support Variant Interpretation Harrison SM, Riggs ER, Maglott DR, Lee JM, Azzariti DR, Niehaus A, Ramos EM, Martin CL, Landrum MJ, Rehm HL Curr Protoc Hum Genet 2016 Apr 1;89:8 PMID 27037489 Identification and analysis of deleterious human SNPs Yue P, Moult J J Mol Biol 2006 Mar 10;356(5):1263-74 PMID 16412461 The NIH genetic testing registry: a new, centralized database of genetic tests to enable access to comprehensive information and improve transparency Rubinstein WS, Maglott DR, Lee JM, Kattman BL, Malheiro AJ, Ovetsky M, Hem V, Gorelenkov V, Song G, Wallin C, Husain N, Chitipiralla S, Katz KS, Hoffman D, Jang W, Johnson M, Karmanov F, Ukrainchik A, Denisenko M, Fomous C, Hudson K, Ostell JM Nucleic Acids Res 2013 Jan;41(Database issue):D925-35 PMID 23193275 Reference sequence (RefSeq) database at NCBI: current status, taxonomic expansion, and functional annotation O'Leary NA, Wright MW, Brister JR, Ciufo S, Haddad D, McVeigh R, Rajput B, Robbertse B, Smith-White B, Ako-Adjei D, Astashyn A, Badretdin A, Bao Y, Blinkova O, Brover V, Chetvernin V, Choi J, Cox E, Ermolaeva O, Farrell CM, Goldfarb T, Gupta T, Haft D, Hatcher E, Hlavina W, Joardar VS, Kodali VK, Li W, Maglott D, Masterson P, McGarvey KM, Murphy MR, O'Neill K, Pujar S, Rangwala SH, Rausch D, Riddick LD, Schoch C, Shkeda A, Storz SS, Sun H, Thibaud-Nissen F, Tolstoy I, Tully RE, Vatsan AR, Wallin C, Webb D, Wu W, Landrum MJ, Kimchi A, Tatusova T, DiCuccio M, Kitts P, Murphy TD, Pruitt KD Nucleic Acids Res 2016 Jan 4;44(D1):D733-45 PMID 26553804 The UCSC Genome Browser database: 2015 update Rosenbloom KR, Armstrong J, Barber GP, Casper J, Clawson H, Diekhans M, Dreszer TR, Fujita PA, Guruvadoo L, Haeussler M, Harte RA, Heitner S, Hickey G, Hinrichs AS, Hubley R, Karolchik D, Learned K, Lee BT, Li CH, Miga KH, Nguyen N, Paten B, Raney BJ, Smit AF, Speir ML, Zweig AS, Haussler D, Kuhn RM, Kent WJ Nucleic Acids Res 2015 Jan;43(Database issue):D670-81 PMID 25428374 BioGPS: building your own mash-up of gene annotations and expression profiles Wu C, Jin X, Tsueng G, Afrasiabi C, Su AI Nucleic Acids Res 2016 Jan 4;44(D1):D313-6 PMID 26578587 UniProt: a hub for protein information UniProt Consortium Nucleic Acids Res 2015 Jan;43(Database issue):D204-12 PMID 25348405 The neXtProt knowledgebase on human proteins: current status Gaudet P, Michel PA, Zahn-Zabal M, Cusin I, Duek PD, Evalet O, Gateau A, Gleizes A, Pereira M, Teixeira D, Zhang Y, Lane L, Bairoch A Nucleic Acids Res 2015 Jan;43(Database issue):D764-70 PMID 25593349 PhosphoSitePlus, 2014: mutations, PTMs and recalibrations Hornbeck PV, Zhang B, Murray B, Kornhauser JM, Latham V, Skrzypek E Nucleic Acids Res 2015 Jan;43(Database issue):D512-20 PMID 25514926 New and continuing developments at PROSITE Sigrist CJ, de Castro E, Cerutti L, Cuche BA, Hulo N, Bridge A, Bougueleret L, Xenarios I Nucleic Acids Res 2013 Jan;41(Database issue):D344-7 PMID 23161676 The Pfam protein families database: towards a more sustainable future Finn RD, Coggill P, Eberhardt RY, Eddy SR, Mistry J, Mitchell AL, Potter SC, Punta M, Qureshi M, Sangrador-Vegas A, Salazar GA, Tate J, Bateman A Nucleic Acids Res 2016 Jan 4;44(D1):D279-85 PMID 26673716 The InterPro protein families database: the classification resource after 15 years Mitchell A, Chang HY, Daugherty L, Fraser M, Hunter S, Lopez R, McAnulla C, McMenamin C, Nuka G, Pesseat S, Sangrador-Vegas A, Scheremetjew M, Rato C, Yong SY, Bateman A, Punta M, Attwood TK, Sigrist CJ, Redaschi N, Rivoire C, Xenarios I, Kahn D, Guyot D, Bork P, Letunic I, Gough J, Oates M, Haft D, Huang H, Natale DA, Wu CH, Orengo C, Sillitoe I, Mi H, Thomas PD, Finn RD Nucleic Acids Res 2015 Jan;43(Database issue):D213-21 PMID 25428371 GeneTests: an online genetic information resource for health care providers Pagon RA J Med Libr Assoc 2006 Jul;94(3):343-8 PMID 16888670 Representation of rare diseases in health information systems: the Orphanet approach to serve a wide range of end users Rath A, Olry A, Dhombres F, Brandt MM, Urbero B, Ayme S Hum Mutat 2012 May;33(5):803-8 PMID 22422702 Activation of proto-oncogenes by disruption of chromosome neighborhoods Hnisz D, Weintraub AS, Day DS, Valton AL, Bak RO, Li CH, Goldmann J, Lajoie BR, Fan ZP, Sigova AA, Reddy J, Borges-Rivera D, Lee TI, Jaenisch R, Porteus MH, Dekker J, Young RA Science 2016 Mar 25;351(6280):1454-8 PMID 26940867 Discovery of unfixed endogenous retrovirus insertions in diverse human populations Wildschutte JH, Williams ZH, Montesion M, Subramanian RP, Kidd JM, Coffin JM Proc Natl Acad Sci U S A 2016 Apr 19;113(16):E2326-34 PMID 27001843 All the World's a Stage: Facilitating Discovery Science and Improved Cancer Care through the Global Alliance for Genomics and Health Lawler M, Siu LL, Rehm HL, Chanock SJ, Alterovitz G, Burn J, Calvo F, Lacombe D, Teh BT, North KN, Sawyers CL; Clinical Working Group of the Global Alliance for Genomics and Health (GA4GH) Cancer Discov 2015 Nov;5(11):1133-6 PMID 26526696 Written 2016-04 Etienne De Braekeleer, Jean Loup Huret, Hossain Mossafa, Katriina Hautaviita, Philippe Dessen Cancer Genetics & Stem Cell Genetics, Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, United Kingdom; Medical Genetics, Dept Medical Information, University Hospital, F-86021 Poitiers, France; Laboratoire CERBA, 95310 Saint Ouen l'Aumone, France; (Mouse genomics, Wellcome Trust Sanger Institute); UMR 1170 INSERM, Gustave Roussy, 114 rue Edouard Vaillant, F-94805 Villejuif, France. Citation This paper should be referenced as such : De Braekeleer E, Huret JL, Mossafa H, Hautaviita K, Dessen P Internet databases and resources for cytogenetics and cytogenomic Atlas Genet Cytogenet Oncol Haematol. in press On line version : http://AtlasGeneticsOncology.org/Deep/Internet_DatabasesID20143.htm
© Atlas of Genetics and Cytogenetics in Oncology and Haematology indexed on : Wed Aug 2 16:13:32 CEST 2017
For comments and suggestions or contributions, please contact us