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HRAS (Harvey rat sarcoma viral oncogene homolog)

Written1999-02Franz Watzinger, Thomas Lion
Children's Cancer Research Institute (CCRI), Kinderspitalgasse 6, A-1090 Vienna, Austria

(Note : for Links provided by Atlas : click)

Identity

Alias_namesHRAS1
v-Ha-ras Harvey rat sarcoma viral oncogene homolog
Harvey rat sarcoma viral oncogene homolog
Other aliasc-Ha-ras 1
HGNC (Hugo) HRAS
LocusID (NCBI) 3265
Atlas_Id 108
Location 11p15.5  [Link to chromosome band 11p15]
Location_base_pair Starts at 532242 and ends at 535567 bp from pter ( according to hg19-Feb_2009)  [Mapping HRAS.png]
 
  Probe(s) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics
Fusion genes
(updated 2016)
FYCO1 (3p21.31) / HRAS (11p15.5)RNH1 (11p15.5) / HRAS (11p15.5)
Note more on the RAS family is available as a deep insight.

DNA/RNA

Note to be quoted is the existence of a pseudogene, c-Ha-ras 2, inactivated, processed pseudogene which is located on Chromosome X.
 
  H-ras splicing variants : alternative splicing of H-ras precursor mRNA leads to the two transcripts p19 and p21 which differ by the ex- or inclusion of the Intron D Exon (IDX); Exons that encode protein are shown as black boxes, untranslated exons as white boxes; the upstream untranslated exon is indicated as Exon -1
Description consists of six exons, spread over 6.6kb of genomic DNA
Transcription alternative RNA splicing reveals two different transcripts (see Fig); if the Intron D Exon (IDX) is skipped exon 4 is directly joined to exon 3

Protein

Description regular RAS protein - characterized in the RAS family page
Expression ubiquitously expressed
Localisation anchored to the inner surface of the plasma membrane
Function analogously to other GTP-binding proteins (such as Translation Elongation Factor EFTu or signal transducing G-Proteins) RAS proteins are involved in signal transduction pathways
Homology ras gene family is part of the ras superfamily including the mammalian RAS, RAL, RAC, RHO, RAP, and RAB gene families and the yeast homologs like SEC4 and YPT1 genes; genes encode small monomeric proteins of low molecular mass (20-30 kDa) which share at least 30% homology with RAS proteins.

Implicated in

Note
  
Entity tumor (frequency of H-RAS mutations); references in Full Bibliography
  
  
Entity stomach (0-40%)
  
  
Entity urinary bladder (0-65%)
  
  
Entity prostate (0-10%)
  
  
Entity skin (0-45%)
  
  
Entity thyroid (0-60%)
  
  
Entity breast (0-10%)
  
  
Entity head and neck (0-30%)
  
  
Entity endometrium (5%)
  

Bibliography

ras oncogenes: their role in neoplasia.
Barbacid M
European journal of clinical investigation. 1990 ; 20 (3) : 225-235.
PMID 2114981
 
ras oncogenes in human cancer: a review.
Bos JL
Cancer research. 1989 ; 49 (17) : 4682-4689.
PMID 2547513
 
Variability of Ha-ras (codon 12) proto-oncogene mutations in diverse thyroid cancers.
Bouras M, Bertholon J, Dutrieux-Berger N, Parvaz P, Paulin C, Revol A
European journal of endocrinology / European Federation of Endocrine Societies. 1998 ; 139 (2) : 209-216.
PMID 9724079
 
Codon 12 Harvey-ras mutations are rare events in non-melanoma human skin cancer.
Campbell C, Quinn AG, Rees JL
The British journal of dermatology. 1993 ; 128 (2) : 111-114.
PMID 8096149
 
Ras oncogene mutations in thyroid tumors: polymerase chain reaction-restriction-fragment-length polymorphism analysis from paraffin-embedded tissues.
Capella G, Matias-Guiu X, Ampudia X, de Leiva A, Perucho M, Prat J
Diagnostic molecular pathology : the American journal of surgical pathology, part B. 1996 ; 5 (1) : 45-52.
PMID 8919545
 
ras gene mutations in human prostate cancer.
Carter BS, Epstein JI, Isaacs WB
Cancer research. 1990 ; 50 (21) : 6830-6832.
PMID 2208148
 
The absence of Harvey ras mutations during development and progression of squamous cell carcinomas of the head and neck.
Clark LJ, Edington K, Swan IR, McLay KA, Newlands WJ, Wills LC, Young HA, Johnston PW, Mitchell R, Robertson G
British journal of cancer. 1993 ; 68 (3) : 617-620.
PMID 8353052
 
Expression of the H-ras proto-oncogene is controlled by alternative splicing.
Cohen JB, Broz SD, Levinson AD
Cell. 1989 ; 58 (3) : 461-472.
PMID 2667764
 
Correlation of mutations of oncogene C-Ha-ras at codon 12 with metastasis and survival of gastric cancer patients.
Deng GR, Liu XH, Wang JR
Oncogene research. 1991 ; 6 (1) : 33-38.
PMID 1671796
 
A new oncogene in human thyroid papillary carcinomas and their lymph-nodal metastases.
Fusco A, Grieco M, Santoro M, Berlingieri MT, Pilotti S, Pierotti MA, Della Porta G, Vecchio G
Nature. 1987 ; 328 (6126) : 170-172.
PMID 3600795
 
Activated ras alleles in human carcinoma of the prostate are rare.
Gumerlock PH, Poonamallee UR, Meyers FJ, deVere White RW
Cancer research. 1991 ; 51 (6) : 1632-1637.
PMID 1998954
 
A PCR-RFLP method for the detection of activated H-ras oncogene with a point mutation at codon 12 and 61.
Hong SJ, Lee T, Park YS, Lee KO, Chung BH, Lee SH
Yonsei medical journal. 1996 ; 37 (6) : 371-379.
PMID 9048488
 
A splicing enhancer in the 3'-terminal c-H-ras exon influences mRNA abundance and transforming activity.
Hwang DY, Cohen JB
Journal of virology. 1997 ; 71 (9) : 6416-6426.
PMID 9261359
 
Mutations, expression and genomic instability of the H-ras proto-oncogene in squamous cell carcinomas of the head and neck.
Kiaris H, Spandidos DA, Jones AS, Vaughan ED, Field JK
British journal of cancer. 1995 ; 72 (1) : 123-128.
PMID 7599040
 
Mutation of ras oncogene in gastric adenocarcinoma: association with histological phenotype.
Kim TY, Bang YJ, Kim WS, Kang SH, Lee KU, Choe KJ, Kim NK
Anticancer research. 1997 ; 17 (2B) : 1335-1339.
PMID 9137494
 
Comparison of ras activation in prostate carcinoma in Japanese and American men.
Konishi N, Hiasa Y, Tsuzuki T, Tao M, Enomoto T, Miller GJ
The Prostate. 1997 ; 30 (1) : 53-57.
PMID 9018336
 
A position 12-activated H-ras oncogene in all HS578T mammary carcinosarcoma cells but not normal mammary cells of the same patient.
Kraus MH, Yuasa Y, Aaronson SA
Proceedings of the National Academy of Sciences of the United States of America. 1984 ; 81 (17) : 5384-5388.
PMID 6089200
 
High frequency of ras oncogene activation in all stages of human thyroid tumorigenesis.
Lemoine NR, Mayall ES, Wyllie FS, Williams ED, Goyns M, Stringer B, Wynford-Thomas D
Oncogene. 1989 ; 4 (2) : 159-164.
PMID 2648253
 
Oncogenes and bladder cancer.
Malone PR, Visvanathan KV, Ponder BA, Shearer RJ, Summerhayes IC
British journal of urology. 1985 ; 57 (6) : 664-667.
PMID 4084726
 
ras activation in experimental carcinogenesis.
Mangues R, Pellicer A
Seminars in cancer biology. 1992 ; 3 (4) : 229-239.
PMID 1421167
 
K-ras activation in gastric epithelial tumors in Japanese.
Miki H, Ohmori M, Perantoni AO, Enomoto T
Cancer letters. 1991 ; 58 (1-2) : 107-113.
PMID 2049776
 
Infrequent point mutations of ras oncogenes in gastric cancers.
Nanus DM, Kelsen DP, Mentle IR, Altorki N, Albino AP
Gastroenterology. 1990 ; 98 (4) : 955-960.
PMID 2179035
 
Human cancer and cellular oncogenes.
Nishimura S, Sekiya T
The Biochemical journal. 1987 ; 243 (2) : 313-327.
PMID 3307760
 
Low-frequency mutation of Ha-ras and Ki-ras oncogenes in transitional cell carcinoma of the bladder.
Older&oring; G, Daehlin L, Ogreid D
Anticancer research. 1998 ; 18 (4A) : 2675-2678.
PMID 9703927
 
Low incidence of ras oncogene activation in human squamous cell carcinomas.
Rumsby G, Carter RL, Gusterson BA
British journal of cancer. 1990 ; 61 (3) : 365-368.
PMID 2183872
 
Screening of H-ras gene point mutations in 50 cases of bladder carcinoma.
Saito S, Hata M, Fukuyama R, Sakai K, Kudoh J, Tazaki H, Shimizu N
International journal of urology : official journal of the Japanese Urological Association. 1997 ; 4 (2) : 178-185.
PMID 9179693
 
High frequency mutation in codons 12 and 61 of H-ras oncogene in chewing tobacco-related human oral carcinoma in India.
Saranath D, Chang SE, Bhoite LT, Panchal RG, Kerr IB, Mehta AR, Johnson NW, Deo MG
British journal of cancer. 1991 ; 63 (4) : 573-578.
PMID 2021541
 
Mutations of ras genes are relatively frequent in Japanese prostate cancers: pointing to genetic differences between populations.
Shiraishi T, Muneyuki T, Fukutome K, Ito H, Kotake T, Watanabe M, Yatani R
Anticancer research. 1998 ; 18 (4B) : 2789-2792.
PMID 9713462
 
Oncogene activation in malignant transformation: a study of H-ras in human breast cancer.
Spandidos DA
Anticancer research. 1987 ; 7 (5B) : 991-996.
PMID 3435051
 
Detection of activated ras oncogenes in human thyroid carcinomas.
Su´rez HG, Du Villard JA, Caillou B, Schlumberger M, Tubiana M, Parmentier C, Monier R
Oncogene. 1988 ; 2 (4) : 403-406.
PMID 3283656
 
Mapping of UV photoproducts within ras proto-oncogenes in UV-irradiated cells: correlation with mutations in human skin cancer.
Törmä VT, Pfeifer GP
Oncogene. 1992 ; 7 (9) : 1729-1736.
PMID 1501884
 
ras gene mutations in human endometrial carcinoma.
Varras MN, Koffa M, Koumantakis E, Ergazaki M, Protopapa E, Michalas S, Spandidos DA
Oncology. 1996 ; 53 (6) : 505-510.
PMID 8960147
 
No evidence for point mutations in codons 12, 13, and 61 of the ras gene in a high-incidence area for esophageal and gastric cancers.
Victor T, Du Toit R, Jordaan AM, Bester AJ, van Helden PD
Cancer research. 1990 ; 50 (16) : 4911-4914.
PMID 2199031
 
Preferential and novel activation of H-ras in human bladder carcinomas.
Visvanathan KV, Pocock RD, Summerhayes IC
Oncogene research. 1988 ; 3 (1) : 77-86.
PMID 3144694
 

Citation

This paper should be referenced as such :
Watzinger, F ; Lion, T
HRAS (Harvey rat sarcoma viral oncogene homolog)
Atlas Genet Cytogenet Oncol Haematol. 1999;3(2):63-65.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/HRASID108.html


Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 16 ]
  Thyroid: Anaplastic (undifferentiated) carcinoma
Bladder: Urothelial carcinomas
Breast tumors : an overview
Colon: Colorectal adenocarcinoma
Bone: Dedifferentiated chondrosarcoma
Breast: Ductal carcinoma
Soft Tissues: Embryonal rhabdomyosarcoma
Head and Neck: Epidermoid carcinoma
Head and Neck: Iris Hamartomas
Thyroid: Medullary carcinoma
Ovary: Epithelial tumors
Soft Tissues: Rhabdomyosarcoma
Skin: Melanoma
Testis: Spermatocytic seminoma
Skin: Spitz tumors
Thyroid: Papillary carcinoma with inv(10)(p12.1q11.2) ACBD5/RET


Other Cancer prone implicated (Data extracted from papers in the Atlas) [ 1 ]
  Costello syndrome


External links

Nomenclature
HGNC (Hugo)HRAS   5173
LRG (Locus Reference Genomic)LRG_506
Cards
AtlasHRASID108
Entrez_Gene (NCBI)HRAS  3265  HRas proto-oncogene, GTPase
AliasesC-BAS/HAS; C-H-RAS; C-HA-RAS1; CTLO; 
H-RASIDX; HAMSV; HRAS1; RASH1; p21ras
GeneCards (Weizmann)HRAS
Ensembl hg19 (Hinxton)ENSG00000174775 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000174775 [Gene_View]  chr11:532242-535567 [Contig_View]  HRAS [Vega]
ICGC DataPortalENSG00000174775
TCGA cBioPortalHRAS
AceView (NCBI)HRAS
Genatlas (Paris)HRAS
WikiGenes3265
SOURCE (Princeton)HRAS
Genetics Home Reference (NIH)HRAS
Genomic and cartography
GoldenPath hg38 (UCSC)HRAS  -     chr11:532242-535567 -  11p15.5   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)HRAS  -     11p15.5   [Description]    (hg19-Feb_2009)
EnsemblHRAS - 11p15.5 [CytoView hg19]  HRAS - 11p15.5 [CytoView hg38]
Mapping of homologs : NCBIHRAS [Mapview hg19]  HRAS [Mapview hg38]
OMIM109800   137550   162900   163200   188470   190020   218040   
Gene and transcription
Genbank (Entrez)AB451336 AB451485 AF493916 AJ437024 BC006499
RefSeq transcript (Entrez)NM_001130442 NM_001318054 NM_005343 NM_176795
RefSeq genomic (Entrez)NC_000011 NC_018922 NG_007666 NT_187586
Consensus coding sequences : CCDS (NCBI)HRAS
Cluster EST : UnigeneHs.37003 [ NCBI ]
CGAP (NCI)Hs.37003
Alternative Splicing GalleryENSG00000174775
Gene ExpressionHRAS [ NCBI-GEO ]   HRAS [ EBI - ARRAY_EXPRESS ]   HRAS [ SEEK ]   HRAS [ MEM ]
Gene Expression Viewer (FireBrowse)HRAS [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)3265
GTEX Portal (Tissue expression)HRAS
Protein : pattern, domain, 3D structure
UniProt/SwissProtP01112   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP01112  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP01112
Splice isoforms : SwissVarP01112
PhosPhoSitePlusP01112
Domaine pattern : Prosite (Expaxy)RAS (PS51421)   
Domains : Interpro (EBI)P-loop_NTPase    Small_GTP-bd_dom    Small_GTPase    Small_GTPase_Ras   
Domain families : Pfam (Sanger)Ras (PF00071)   
Domain families : Pfam (NCBI)pfam00071   
Conserved Domain (NCBI)HRAS
DMDM Disease mutations3265
Blocks (Seattle)HRAS
PDB (SRS)###############################################################################################################################################################################################################################################################   
PDB (PDBSum)###############################################################################################################################################################################################################################################################   
PDB (IMB)###############################################################################################################################################################################################################################################################   
PDB (RSDB)###############################################################################################################################################################################################################################################################   
Structural Biology KnowledgeBase###############################################################################################################################################################################################################################################################   
SCOP (Structural Classification of Proteins)###############################################################################################################################################################################################################################################################   
CATH (Classification of proteins structures)###############################################################################################################################################################################################################################################################   
SuperfamilyP01112
Human Protein AtlasENSG00000174775
Peptide AtlasP01112
HPRD01813
IPIIPI00000006   IPI00741763   IPI00979370   
Protein Interaction databases
DIP (DOE-UCLA)P01112
IntAct (EBI)P01112
FunCoupENSG00000174775
BioGRIDHRAS
STRING (EMBL)HRAS
ZODIACHRAS
Ontologies - Pathways
QuickGOP01112
Ontology : AmiGOGolgi membrane  MAPK cascade  positive regulation of protein phosphorylation  stimulatory C-type lectin receptor signaling pathway  GTPase activity  GTPase activity  protein binding  GTP binding  GTP binding  nucleus  cytoplasm  Golgi apparatus  cytosol  plasma membrane  plasma membrane  endocytosis  chemotaxis  cell cycle arrest  cell cycle arrest  mitotic cell cycle checkpoint  signal transduction  cell surface receptor signaling pathway  epidermal growth factor receptor signaling pathway  Ras protein signal transduction  Ras protein signal transduction  axon guidance  protein C-terminus binding  cell proliferation  positive regulation of cell proliferation  negative regulation of cell proliferation  animal organ morphogenesis  negative regulation of gene expression  GDP binding  positive regulation of cell migration  positive regulation of interferon-gamma production  negative regulation of GTPase activity  response to isolation stress  Fc-epsilon receptor signaling pathway  ERBB2 signaling pathway  T-helper 1 type immune response  defense response to protozoan  positive regulation of MAP kinase activity  positive regulation of MAPK cascade  negative regulation of neuron apoptotic process  positive regulation of GTPase activity  positive regulation of DNA replication  positive regulation of transcription from RNA polymerase II promoter  positive regulation of JNK cascade  positive regulation of Ras protein signal transduction  ephrin receptor signaling pathway  regulation of long-term neuronal synaptic plasticity  perinuclear region of cytoplasm  positive regulation of epithelial cell proliferation  T cell receptor signaling pathway  leukocyte migration  protein heterooligomerization  positive regulation of ERK1 and ERK2 cascade  cellular response to gamma radiation  positive regulation of wound healing  cellular senescence  intrinsic apoptotic signaling pathway  positive regulation of ruffle assembly  positive regulation of actin cytoskeleton reorganization  positive regulation of miRNA metabolic process  
Ontology : EGO-EBIGolgi membrane  MAPK cascade  positive regulation of protein phosphorylation  stimulatory C-type lectin receptor signaling pathway  GTPase activity  GTPase activity  protein binding  GTP binding  GTP binding  nucleus  cytoplasm  Golgi apparatus  cytosol  plasma membrane  plasma membrane  endocytosis  chemotaxis  cell cycle arrest  cell cycle arrest  mitotic cell cycle checkpoint  signal transduction  cell surface receptor signaling pathway  epidermal growth factor receptor signaling pathway  Ras protein signal transduction  Ras protein signal transduction  axon guidance  protein C-terminus binding  cell proliferation  positive regulation of cell proliferation  negative regulation of cell proliferation  animal organ morphogenesis  negative regulation of gene expression  GDP binding  positive regulation of cell migration  positive regulation of interferon-gamma production  negative regulation of GTPase activity  response to isolation stress  Fc-epsilon receptor signaling pathway  ERBB2 signaling pathway  T-helper 1 type immune response  defense response to protozoan  positive regulation of MAP kinase activity  positive regulation of MAPK cascade  negative regulation of neuron apoptotic process  positive regulation of GTPase activity  positive regulation of DNA replication  positive regulation of transcription from RNA polymerase II promoter  positive regulation of JNK cascade  positive regulation of Ras protein signal transduction  ephrin receptor signaling pathway  regulation of long-term neuronal synaptic plasticity  perinuclear region of cytoplasm  positive regulation of epithelial cell proliferation  T cell receptor signaling pathway  leukocyte migration  protein heterooligomerization  positive regulation of ERK1 and ERK2 cascade  cellular response to gamma radiation  positive regulation of wound healing  cellular senescence  intrinsic apoptotic signaling pathway  positive regulation of ruffle assembly  positive regulation of actin cytoskeleton reorganization  positive regulation of miRNA metabolic process  
Pathways : BIOCARTA [Genes]   
Pathways : KEGG   
REACTOMEP01112 [protein]
REACTOME PathwaysR-HSA-8853338 [pathway]   
NDEx NetworkHRAS
Atlas of Cancer Signalling NetworkHRAS
Wikipedia pathwaysHRAS
Orthology - Evolution
OrthoDB3265
GeneTree (enSembl)ENSG00000174775
Phylogenetic Trees/Animal Genes : TreeFamHRAS
HOVERGENP01112
HOGENOMP01112
Homologs : HomoloGeneHRAS
Homology/Alignments : Family Browser (UCSC)HRAS
Gene fusions - Rearrangements
Fusion : MitelmanRNH1/HRAS [11p15.5/11p15.5]  [t(11;11)(p15;p15)]  
Fusion: TCGARNH1 11p15.5 HRAS 11p15.5 HNSC
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerHRAS [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)HRAS
dbVarHRAS
ClinVarHRAS
1000_GenomesHRAS 
Exome Variant ServerHRAS
ExAC (Exome Aggregation Consortium)HRAS (select the gene name)
Genetic variants : HAPMAP3265
Genomic Variants (DGV)HRAS [DGVbeta]
DECIPHERHRAS [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisHRAS 
Mutations
ICGC Data PortalHRAS 
TCGA Data PortalHRAS 
Broad Tumor PortalHRAS
OASIS PortalHRAS [ Somatic mutations - Copy number]
Cancer Gene: CensusHRAS 
Somatic Mutations in Cancer : COSMICHRAS  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDHRAS
intOGen PortalHRAS
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
LOVD (Leiden Open Variation Database)MSeqDR-LSDB Mitochondrial Disease Locus Specific Database
BioMutasearch HRAS
DgiDB (Drug Gene Interaction Database)HRAS
DoCM (Curated mutations)HRAS (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)HRAS (select a term)
intoGenHRAS
NCG5 (London)HRAS
Cancer3DHRAS(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM109800    137550    162900    163200    188470    190020    218040   
Orphanet549    574    905    2605   
MedgenHRAS
Genetic Testing Registry HRAS
NextProtP01112 [Medical]
TSGene3265
GENETestsHRAS
Target ValidationHRAS
Huge Navigator HRAS [HugePedia]
snp3D : Map Gene to Disease3265
BioCentury BCIQHRAS
ClinGenHRAS (curated)
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD3265
Chemical/Pharm GKB GenePA29444
Drug Sensitivity HRAS
Clinical trialHRAS
Miscellaneous
canSAR (ICR)HRAS (select the gene name)
Other databasehttp://cancergenome.broadinstitute.org/index.php?tgene=HRAS
Probes
Litterature
PubMed499 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineHRAS
EVEXHRAS
GoPubMedHRAS
iHOPHRAS
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Fri Jun 30 11:08:41 CEST 2017

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