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RELA (v-rel reticuloendotheliosis viral oncogene homolog A (avian))

Written2002-01Fei Chen
Health Effects Laboratory Division, NIOSH, 1095 Willowdale Rd, Morgantown, WV 26505, USA

(Note : for Links provided by Atlas : click)

Identity

Other namesNFKB3
p65
HGNC (Hugo) RELA
LocusID (NCBI) 5970
Atlas_Id 325
Location 11q13.1
Location_base_pair Starts at 65421067 and ends at 65430443 bp from pter ( according to hg19-Feb_2009)  [Mapping]
 
  Probe(s) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics
Fusion genes
(updated 2016)
ACTB (7p22.1) / RELA (11q13.1)C11orf95 (11q13.1) / RELA (11q13.1)LGALS4 (19q13.2) / RELA (11q13.1)
RELA (11q13.1) / C16orf45 (16p13.11)ZMYND8 (20q13.12) / RELA (11q13.1)
Note see also, in the Deep Insight section: Upstream Signal Transduction of NF-kB Activation

DNA/RNA

Description The gene encoding human RelA has 10 exons spanning 8.1 kb. The shorter variants of RelA (p65d) can be generated by alternative splicing of intron 1, 6, or 7. The p65d1 lacks codons for amino acids 222 to 231 and p65d2 lacks codons for amino acids 13 to 25 of the conserved Rel homology domain. An additional alternative splicing form of p65, p65d3 has been identified in a non-small-cell lung carcinoma cell line that lacks codons for amino acids 187 to 293 of the Rel homology domain.

Protein

Description The relA gene encodes a protein composed 551 amino acids with an approximately molecular weight of 65 kDa. The N-terminal region of RelA contains a Rel homology domain (RHD) followed by a nuclear localization signal. The C-terminal region of RelA contains a putative leucine zipper domain and a transactivation domain that is important for the NF-kB-mediated gene transactivation. A number of protein kinases can phosphorylate RelA and consequently potentiate the transcriptional activity of NF-kB complexes. These kinases include IKKb, PKA, and possibly GSK3 and MAP kinase p38. The phosphorylation of the transactivation domain of RelA was considered as an important event for the recruitment and/or interaction with co-factors and general transcriptional machinery subunits such as p300 and TFIIB.
Expression wide.
Localisation cytosol, nuclei after activation.
Function regulation of the genes involved in cell-to-cell interaction, intercellular communication, cell recruitment or transmigration, amplification or spreading of primary pathogenic signals, cell apoptosis, and initiation or acceleration of tumorigenesis. The p50/RelA complex is the most abundant NF-kB complex in all type tissues or cells. Interaction with: members of IkB family and Rel family; GR; HDAC3; CREB; p300; Sp1, Egr1; AES; TFIIB.

Implicated in

Note
Entity cancer, autoimmune arthritis, glomerulonephritis, asthma, inflammatory bowel disease, septic shock, lung fibrosis, HTLV-1 infection, and AIDS.
Oncogenesis Chromosomal rearrangement or point mutation of relA gene has been implicated infrequently in human lymphoid tumors. A t(11;14)(q14;q32?) chromosomal translocation was described in 4 cases of lymphoproliferative disorders (LPD), which possibly involved p65 gene rearrangement. Gene amplification or increased expression of relA has also been noted in some cases of squamous carcinomas of head and neck, and in adenocarcinomas of breast and stomach.
  

Bibliography

A new characteristic karyotypic anomaly in lymphoproliferative disorders.
Van Den Berghe H, Parloir C, David G, Michaux JL, Sokal G
Cancer. 1979 ; 44 (1) : 188-195.
PMID 582293
 
The NF-kappa B and I kappa B proteins: new discoveries and insights.
Baldwin AS Jr
Annual review of immunology. 1996 ; 14 : 649-683.
PMID 8717528
 
NF-kappa B and Rel proteins: evolutionarily conserved mediators of immune responses.
Ghosh S, May MJ, Kopp EB
Annual review of immunology. 1998 ; 16 : 225-260.
PMID 9597130
 
Genomic organization of the gene encoding the p65 subunit of NF-kappa B: multiple variants of the p65 protein may be generated by alternative splicing.
Deloukas P, van Loon AP
Human molecular genetics. 1993 ; 2 (11) : 1895-1900.
PMID 8281153
 
Phosphorylation of NF-kappa B p65 by PKA stimulates transcriptional activity by promoting a novel bivalent interaction with the coactivator CBP/p300.
Zhong H, Voll RE, Ghosh S
Molecular cell. 1998 ; 1 (5) : 661-671.
PMID 9660950
 
Aberrant rel/nfkb genes and activity in human cancer.
Rayet B, Gélinas C
Oncogene. 1999 ; 18 (49) : 6938-6947.
PMID 10602468
 

Citation

This paper should be referenced as such :
Chen, F
RELA (v-rel reticuloendotheliosis viral oncogene homolog A)
Atlas Genet Cytogenet Oncol Haematol. 2002;6(2):100-101.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/RELAID325.html


External links

Nomenclature
HGNC (Hugo)RELA   9955
Cards
AtlasRELAID325
Entrez_Gene (NCBI)RELA  5970  v-rel avian reticuloendotheliosis viral oncogene homolog A
GeneCards (Weizmann)RELA
Ensembl hg19 (Hinxton)ENSG00000173039 [Gene_View]  chr11:65421067-65430443 [Contig_View]  RELA [Vega]
Ensembl hg38 (Hinxton)ENSG00000173039 [Gene_View]  chr11:65421067-65430443 [Contig_View]  RELA [Vega]
ICGC DataPortalENSG00000173039
TCGA cBioPortalRELA
AceView (NCBI)RELA
Genatlas (Paris)RELA
WikiGenes5970
SOURCE (Princeton)RELA
Genomic and cartography
GoldenPath hg19 (UCSC)RELA  -     chr11:65421067-65430443 -  11q13   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)RELA  -     11q13   [Description]    (hg38-Dec_2013)
EnsemblRELA - 11q13 [CytoView hg19]  RELA - 11q13 [CytoView hg38]
Mapping of homologs : NCBIRELA [Mapview hg19]  RELA [Mapview hg38]
OMIM164014   
Gene and transcription
Genbank (Entrez)AK303262 AK308020 AK308478 BC011603 BC014095
RefSeq transcript (Entrez)NM_001145138 NM_001243984 NM_001243985 NM_021975
RefSeq genomic (Entrez)NC_000011 NC_018922 NG_029971 NT_167190 NW_004929380
Consensus coding sequences : CCDS (NCBI)RELA
Cluster EST : UnigeneHs.502875 [ NCBI ]
CGAP (NCI)Hs.502875
Alternative Splicing GalleryENSG00000173039
Gene ExpressionRELA [ NCBI-GEO ]   RELA [ EBI - ARRAY_EXPRESS ]   RELA [ SEEK ]   RELA [ MEM ]
Gene Expression Viewer (FireBrowse)RELA [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)5970
GTEX Portal (Tissue expression)RELA
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ04206 (Uniprot)
NextProtQ04206  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ04206
Splice isoforms : SwissVarQ04206 (Swissvar)
PhosPhoSitePlusQ04206
Domaine pattern : Prosite (Expaxy)REL_1 (PS01204)    REL_2 (PS50254)   
Domains : Interpro (EBI)Ig-like_fold    Ig_E-set    IPT    NFkB/Dor    p53-like_TF_DNA-bd    RelA    RHD_CS    RHD_dimer    RHD_DNA_bind_dom   
Domain families : Pfam (Sanger)RHD_dimer (PF16179)    RHD_DNA_bind (PF00554)   
Domain families : Pfam (NCBI)pfam16179    pfam00554   
Domain families : Smart (EMBL)IPT (SM00429)  
DMDM Disease mutations5970
Blocks (Seattle)RELA
PDB (SRS)1NFI    2LSP    2O61    3GUT    3QXY    3RC0    4KV1    4KV4   
PDB (PDBSum)1NFI    2LSP    2O61    3GUT    3QXY    3RC0    4KV1    4KV4   
PDB (IMB)1NFI    2LSP    2O61    3GUT    3QXY    3RC0    4KV1    4KV4   
PDB (RSDB)1NFI    2LSP    2O61    3GUT    3QXY    3RC0    4KV1    4KV4   
Structural Biology KnowledgeBase1NFI    2LSP    2O61    3GUT    3QXY    3RC0    4KV1    4KV4   
SCOP (Structural Classification of Proteins)1NFI    2LSP    2O61    3GUT    3QXY    3RC0    4KV1    4KV4   
CATH (Classification of proteins structures)1NFI    2LSP    2O61    3GUT    3QXY    3RC0    4KV1    4KV4   
SuperfamilyQ04206
Human Protein AtlasENSG00000173039
Peptide AtlasQ04206
HPRD01241
IPIIPI00386448   IPI00219084   IPI00479470   IPI00884950   IPI00984552   IPI00883897   IPI00977976   IPI00981642   IPI00976323   IPI00978687   IPI00985132   IPI00983349   IPI00976808   IPI00981038   IPI00977443   IPI00979203   IPI00975646   IPI00982760   
Protein Interaction databases
DIP (DOE-UCLA)Q04206
IntAct (EBI)Q04206
FunCoupENSG00000173039
BioGRIDRELA
STRING (EMBL)RELA
ZODIACRELA
Ontologies - Pathways
QuickGOQ04206
Ontology : AmiGOnegative regulation of transcription from RNA polymerase II promoter  RNA polymerase II regulatory region sequence-specific DNA binding  RNA polymerase II core promoter proximal region sequence-specific DNA binding  RNA polymerase II distal enhancer sequence-specific DNA binding  transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding  transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding  transcriptional activator activity, RNA polymerase II distal enhancer sequence-specific binding  liver development  hair follicle development  stimulatory C-type lectin receptor signaling pathway  DNA binding  DNA binding  chromatin binding  transcription factor activity, sequence-specific DNA binding  transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding  protein binding  nucleus  nucleoplasm  transcription factor complex  cytoplasm  cytosol  cytosol  acetaldehyde metabolic process  transcription from RNA polymerase II promoter  inflammatory response  cellular defense response  aging  transcription factor binding  positive regulation of cell proliferation  organ morphogenesis  response to organic substance  response to UV-B  positive regulation of Schwann cell differentiation  viral process  cytokine-mediated signaling pathway  protein kinase binding  membrane protein intracellular domain proteolysis  chromatin DNA binding  ubiquitin protein ligase binding  positive regulation of chondrocyte differentiation  protein complex binding  positive regulation of type I interferon production  response to muramyl dipeptide  response to progesterone  response to insulin  I-kappaB/NF-kappaB complex  response to cobalamin  activating transcription factor binding  cellular response to hepatocyte growth factor stimulus  response to muscle stretch  Fc-epsilon receptor signaling pathway  negative regulation of protein catabolic process  phosphate ion binding  response to drug  identical protein binding  identical protein binding  protein homodimerization activity  actinin binding  histone deacetylase binding  negative regulation of apoptotic process  negative regulation of apoptotic process  positive regulation of I-kappaB kinase/NF-kappaB signaling  response to amino acid  response to morphine  transcription regulatory region DNA binding  positive regulation of interleukin-12 biosynthetic process  negative regulation of transcription, DNA-templated  positive regulation of transcription, DNA-templated  positive regulation of transcription from RNA polymerase II promoter  positive regulation of transcription from RNA polymerase II promoter  negative regulation of insulin receptor signaling pathway  protein heterodimerization activity  protein N-terminus binding  regulation of inflammatory response  T cell receptor signaling pathway  NF-kappaB binding  positive regulation of NF-kappaB transcription factor activity  positive regulation of NF-kappaB transcription factor activity  response to cAMP  defense response to virus  cellular response to hydrogen peroxide  nucleotide-binding oligomerization domain containing 2 signaling pathway  repressing transcription factor binding  response to interleukin-1  NF-kappaB complex  cellular response to lipopolysaccharide  cellular response to nicotine  cellular response to interleukin-1  cellular response to interleukin-6  cellular response to tumor necrosis factor  cellular response to peptide hormone stimulus  ankyrin repeat binding  negative regulation of NIK/NF-kappaB signaling  positive regulation of miRNA metabolic process  negative regulation of extrinsic apoptotic signaling pathway  
Ontology : EGO-EBInegative regulation of transcription from RNA polymerase II promoter  RNA polymerase II regulatory region sequence-specific DNA binding  RNA polymerase II core promoter proximal region sequence-specific DNA binding  RNA polymerase II distal enhancer sequence-specific DNA binding  transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding  transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding  transcriptional activator activity, RNA polymerase II distal enhancer sequence-specific binding  liver development  hair follicle development  stimulatory C-type lectin receptor signaling pathway  DNA binding  DNA binding  chromatin binding  transcription factor activity, sequence-specific DNA binding  transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding  protein binding  nucleus  nucleoplasm  transcription factor complex  cytoplasm  cytosol  cytosol  acetaldehyde metabolic process  transcription from RNA polymerase II promoter  inflammatory response  cellular defense response  aging  transcription factor binding  positive regulation of cell proliferation  organ morphogenesis  response to organic substance  response to UV-B  positive regulation of Schwann cell differentiation  viral process  cytokine-mediated signaling pathway  protein kinase binding  membrane protein intracellular domain proteolysis  chromatin DNA binding  ubiquitin protein ligase binding  positive regulation of chondrocyte differentiation  protein complex binding  positive regulation of type I interferon production  response to muramyl dipeptide  response to progesterone  response to insulin  I-kappaB/NF-kappaB complex  response to cobalamin  activating transcription factor binding  cellular response to hepatocyte growth factor stimulus  response to muscle stretch  Fc-epsilon receptor signaling pathway  negative regulation of protein catabolic process  phosphate ion binding  response to drug  identical protein binding  identical protein binding  protein homodimerization activity  actinin binding  histone deacetylase binding  negative regulation of apoptotic process  negative regulation of apoptotic process  positive regulation of I-kappaB kinase/NF-kappaB signaling  response to amino acid  response to morphine  transcription regulatory region DNA binding  positive regulation of interleukin-12 biosynthetic process  negative regulation of transcription, DNA-templated  positive regulation of transcription, DNA-templated  positive regulation of transcription from RNA polymerase II promoter  positive regulation of transcription from RNA polymerase II promoter  negative regulation of insulin receptor signaling pathway  protein heterodimerization activity  protein N-terminus binding  regulation of inflammatory response  T cell receptor signaling pathway  NF-kappaB binding  positive regulation of NF-kappaB transcription factor activity  positive regulation of NF-kappaB transcription factor activity  response to cAMP  defense response to virus  cellular response to hydrogen peroxide  nucleotide-binding oligomerization domain containing 2 signaling pathway  repressing transcription factor binding  response to interleukin-1  NF-kappaB complex  cellular response to lipopolysaccharide  cellular response to nicotine  cellular response to interleukin-1  cellular response to interleukin-6  cellular response to tumor necrosis factor  cellular response to peptide hormone stimulus  ankyrin repeat binding  negative regulation of NIK/NF-kappaB signaling  positive regulation of miRNA metabolic process  negative regulation of extrinsic apoptotic signaling pathway  
Pathways : BIOCARTACD40L Signaling Pathway [Genes]    Human Cytomegalovirus and Map Kinase Pathways [Genes]    Ceramide Signaling Pathway [Genes]    fMLP induced chemokine gene expression in HMC-1 cells [Genes]    Ras Signaling Pathway [Genes]    Neuropeptides VIP and PACAP inhibit the apoptosis of activated T cells [Genes]    NFkB activation by Nontypeable Hemophilus influenzae [Genes]    Cadmium induces DNA synthesis and proliferation in macrophages [Genes]    Keratinocyte Differentiation [Genes]    Activation of PKC through G protein coupled receptor [Genes]    TNFR2 Signaling Pathway [Genes]    NF-kB Signaling Pathway [Genes]    ATM Signaling Pathway [Genes]    Induction of apoptosis through DR3 and DR4/5 Death Receptors [Genes]    MAPKinase Signaling Pathway [Genes]    Toll-Like Receptor Pathway [Genes]    Acetylation and Deacetylation of RelA in The Nucleus [Genes]    The 4-1BB-dependent immune response [Genes]    Role of EGF Receptor Transactivation by GPCRs in Cardiac Hypertrophy [Genes]    CXCR4 Signaling Pathway [Genes]    Corticosteroids and cardioprotection [Genes]    TACI and BCMA stimulation of B cell immune responses. [Genes]    Chaperones modulate interferon Signaling Pathway [Genes]    HIV-I Nef: negative effector of Fas and TNF [Genes]    Inactivation of Gsk3 by AKT causes accumulation of b-catenin in Alveolar Macrophages [Genes]    Signal transduction through IL1R [Genes]    The information-processing pathway at the IFN-beta enhancer [Genes]    Double Stranded RNA Induced Gene Expression [Genes]    TNF/Stress Related Signaling [Genes]    Mechanism of Gene Regulation by Peroxisome Proliferators via PPARa(alpha) [Genes]    Free Radical Induced Apoptosis [Genes]    Bone Remodelling [Genes]    T Cell Receptor Signaling Pathway [Genes]    AKT Signaling Pathway [Genes]    Influence of Ras and Rho proteins on G1 to S Transition [Genes]    Erythropoietin mediated neuroprotection through NF-kB [Genes]   
Pathways : KEGGMAPK signaling pathway    Ras signaling pathway    Chemokine signaling pathway    NF-kappa B signaling pathway    HIF-1 signaling pathway    PI3K-Akt signaling pathway    Apoptosis    Osteoclast differentiation    Toll-like receptor signaling pathway    NOD-like receptor signaling pathway    RIG-I-like receptor signaling pathway    Cytosolic DNA-sensing pathway    T cell receptor signaling pathway    B cell receptor signaling pathway    TNF signaling pathway    Neurotrophin signaling pathway    Prolactin signaling pathway    Adipocytokine signaling pathway    Non-alcoholic fatty liver disease (NAFLD)    Cocaine addiction    Epithelial cell signaling in Helicobacter pylori infection    Shigellosis    Salmonella infection    Pertussis    Legionellosis    Leishmaniasis    Chagas disease (American trypanosomiasis)    Toxoplasmosis    Amoebiasis    Tuberculosis    Hepatitis C    Hepatitis B    Measles    Influenza A    HTLV-I infection    Herpes simplex infection    Epstein-Barr virus infection    Pathways in cancer    Transcriptional misregulation in cancer    Viral carcinogenesis    Pancreatic cancer    Prostate cancer    Chronic myeloid leukemia    Acute myeloid leukemia    Small cell lung cancer    Inflammatory bowel disease (IBD)   
REACTOMEQ04206 [protein]
REACTOME PathwaysR-HSA-193692 Regulated proteolysis of p75NTR [pathway]
REACTOME PathwaysR-HSA-209560 NF-kB is activated and signals survival [pathway]
REACTOME PathwaysR-HSA-202424 Downstream TCR signaling [pathway]
REACTOME PathwaysR-HSA-5660668 CLEC7A/inflammasome pathway [pathway]
REACTOME PathwaysR-HSA-5607764 CLEC7A (Dectin-1) signaling [pathway]
REACTOME PathwaysR-HSA-2559582 Senescence-Associated Secretory Phenotype (SASP) [pathway]
REACTOME PathwaysR-HSA-1810476 RIP-mediated NFkB activation via ZBP1 [pathway]
REACTOME PathwaysR-HSA-3134963 DEx/H-box helicases activate type I IFN and inflammatory cytokines production [pathway]
REACTOME PathwaysR-HSA-2871837 FCERI mediated NF-kB activation [pathway]
REACTOME PathwaysR-HSA-5603027 IKBKG deficiency causes anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) (via TLR) [pathway]
REACTOME PathwaysR-HSA-448706 Interleukin-1 processing [pathway]
REACTOME PathwaysR-HSA-5603029 IkBA variant leads to EDA-ID [pathway]
REACTOME PathwaysR-HSA-1169091 Activation of NF-kappaB in B cells [pathway]
REACTOME PathwaysR-HSA-381340 Transcriptional regulation of white adipocyte differentiation [pathway]
REACTOME PathwaysR-HSA-5607761 Dectin-1 mediated noncanonical NF-kB signaling [pathway]
REACTOME PathwaysR-HSA-933542 TRAF6 mediated NF-kB activation [pathway]
REACTOME PathwaysR-HSA-5621575 CD209 (DC-SIGN) signaling [pathway]
REACTOME PathwaysR-HSA-445989 TAK1 activates NFkB by phosphorylation and activation of IKKs complex [pathway]
NDEx Network
Atlas of Cancer Signalling NetworkRELA
Wikipedia pathwaysRELA
Orthology - Evolution
OrthoDB5970
GeneTree (enSembl)ENSG00000173039
Phylogenetic Trees/Animal Genes : TreeFamRELA
Homologs : HomoloGeneRELA
Homology/Alignments : Family Browser (UCSC)RELA
Gene fusions - Rearrangements
Fusion : MitelmanC11orf95/RELA [11q13.1/11q13.1]  [t(11;11)(q13;q13)]  
Fusion : MitelmanZMYND8/RELA [20q13.12/11q13.1]  [t(11;20)(q13;q13)]  
Polymorphisms : SNP, variants
NCBI Variation ViewerRELA [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)RELA
dbVarRELA
ClinVarRELA
1000_GenomesRELA 
Exome Variant ServerRELA
ExAC (Exome Aggregation Consortium)RELA (select the gene name)
Genetic variants : HAPMAP5970
Genomic Variants (DGV)RELA [DGVbeta]
Mutations
ICGC Data PortalRELA 
TCGA Data PortalRELA 
Broad Tumor PortalRELA
OASIS PortalRELA [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICRELA 
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
BioMutasearch RELA
DgiDB (Drug Gene Interaction Database)RELA
DoCM (Curated mutations)RELA (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)RELA (select a term)
intoGenRELA
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] 
Diseases
DECIPHER (Syndromes)11:65421067-65430443  ENSG00000173039
CONAN: Copy Number AnalysisRELA 
Mutations and Diseases : HGMDRELA
OMIM164014   
MedgenRELA
Genetic Testing Registry RELA
NextProtQ04206 [Medical]
TSGene5970
GENETestsRELA
Huge Navigator RELA [HugePedia]
snp3D : Map Gene to Disease5970
BioCentury BCIQRELA
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD5970
Chemical/Pharm GKB GenePA296
Clinical trialRELA
Miscellaneous
canSAR (ICR)RELA (select the gene name)
Probes
Litterature
PubMed499 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineRELA
EVEXRELA
GoPubMedRELA
iHOPRELA
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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