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ETV6 (ETS variant gene 6 (TEL oncogene))

Identity

Other namesTEL (translocation ets leukemia)
HGNC (Hugo) ETV6
LocusID (NCBI) 2120
Location 12p13.2
Location_base_pair Starts at 11802788 and ends at 12048325 bp from pter ( according to hg19-Feb_2009)  [Mapping]
 
  ETV6 (12p13.1) in normal cells: clone dJ852F10 - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.

DNA/RNA

Description A member of the ets (E-26 transforming specific) family of transcription factors; the gene spans a region of 240 kb and consists of 8 exons.
Transcription transcription is from telomere to centromere; there are three species of transcripts : 2400kb, 4300kb and 6200 kb; the gene encodes for a 1356 kb cDNA

Protein

 
Description There are two alternative start codons that correspondingly result in two isoforms. Codon 1 gives rise to a 57kDa protein while codon 43 gives rise to a 53 kDa protein. It has been demonstrated that these two isoforms are phosphorylated. ETV6 shares homology at the 5' and 3' ends with other ets family members, namely the helix-loop-helix (HLH) and ETS domains, respectively. HLH domain is encoded by exons 3 and 4 and has also been referred to as the pointed or sterile alpha motif (SAM) domain. It is responsible for hetero- and homodimerization with other ETV6 proteins and possibly other ets family members. The ETS domain is encoded by exons 6 through 8 and is responsible for sequence specific DNA-binding. It is positively charged, allowing it to bind to purine rich segments of DNA. A central domain also exists that is involved in the recruitment of a repression complex including NCOR2 and SIN3.
Expression Expression arrays and Northern analysis have shown ubiquitous expression with greater expression in bone marrow, spleen and thymus.
Localisation Immunofluorescence has shown a nuclear localization
Function Acts as a transcriptional regulator; important in vitelline angiogenesis and in bone marrow hematopoiesis.

Mutations

Note ETV6 is implicated in leukemia, myelodysplastic syndromes and sarcoma

Implicated in

  
Entity t(1;12)(p36;p13) --> MDS2/ETV6
Disease One CML with t(9;22) and one refractory anemia with excess of blasts in transformation.
  
Entity t(1;12)(q21;p13) --> ARNT/ETV6
Disease AML-M2
  
Entity t(1;12)(q25;p13) --> ABL2/ETV6
Disease AML-M3, -M4, T-cell ALL
  
Entity t(3;12)(q26;p13) --> EVI1/ETV6
Disease CML
  
Entity t(4;12) (p16;p13) --> FGFR3/ETV6
Disease Peripheral T-cell lymphoma
  
Entity t(4;12)(q11;p13) --> CHIC2 (BTL)/ETV6
Disease AML (FAB type M0)
  
Entity t(5;12)(q31;p13) --> FACL6/ETV6
Disease Acute myelogenous leukemia with eosinophilia
  
Entity t(5;12)(q33;p13) --> PDGFRb/ETV6
Disease CMML
  
Entity t(6;12)(q23;p13) --> STL/ETV6
Disease B-cell ALL
  
Entity t(7;12)(q36;p13) --> HLXB9/ETV6
Disease AML (FAB type M1)
  
Entity dic(9;12)(p13;p13) --> PAX5/ETV6
Disease ALL
  
Entity t(9;12) (p24;p13) --> JAK2/ETV6
Disease Leukemias
  
Entity t(9;12)(q22;p13) --> SYK/ETV6
Disease MDS
  
Entity t(9;12)(q34;p13) --> ABL1/ETV6
Disease Acute myeloblastic leukemia (AML), chronic myelogenous leukemia (CML), acute lymphocytic leukemia (ALL)
  
Entity t(10;12)(q24;p13) --> ?/ETV6
Disease CMML
  
Entity t(12;13)(p13;q12) --> ETV6/ CDX2
Disease CML in transformation, myelodysplastic syndrome (MDS), acute non lymphocytic leukemai (ANLL), B and T- ALL
  
Entity t(12;13)(p13;q14) --> ETV6/ TTL
Disease ALL
  
Entity t(12;15)(p13;q25) --> ETV6 / NTRK3
Disease Congenital Fibrosarcoma, Congenital Mesoblastic Nephroma (cellular and mixed variants), Secretory Ductal Carcinoma of Breast, AML.
  
Entity t(12;17)(p13;p12-p13) --> ETV6 / PER1
Disease AML
  
Entity t(12;21)(p13;q22) --> ETV6 / AML1
Disease Childhood B-cell (ALL)
  
Entity t(12;22)(p13;q11) --> ETV6 / MN1
Disease Refractory Anemia with Excess Blasts
  

Breakpoints

 

External links

Nomenclature
HGNC (Hugo)ETV6   3495
Cards
AtlasETV6ID38
Entrez_Gene (NCBI)ETV6  2120  ets variant 6
GeneCards (Weizmann)ETV6
Ensembl (Hinxton)ENSG00000139083 [Gene_View]  chr12:11802788-12048325 [Contig_View]  ETV6 [Vega]
AceView (NCBI)ETV6
Genatlas (Paris)ETV6
WikiGenes2120
SOURCE (Princeton)NM_001987
Genomic and cartography
GoldenPath (UCSC)ETV6  -  12p13.2   chr12:11802788-12048325 +  12p13   [Description]    (hg19-Feb_2009)
EnsemblETV6 - 12p13 [CytoView]
Mapping of homologs : NCBIETV6 [Mapview]
OMIM131440   600618   601626   
Gene and transcription
Genbank (Entrez)AA205762 AA452592 AI660081 AK289441 AV722693
RefSeq transcript (Entrez)NM_001987
RefSeq genomic (Entrez)AC_000144 NC_000012 NC_018923 NG_011443 NT_009714 NW_001838052 NW_004929383
Consensus coding sequences : CCDS (NCBI)ETV6
Cluster EST : UnigeneHs.504765 [ NCBI ]
CGAP (NCI)Hs.504765
Alternative Splicing : Fast-db (Paris)GSHG0006485
Alternative Splicing GalleryENSG00000139083
Gene ExpressionETV6 [ NCBI-GEO ]     ETV6 [ SEEK ]   ETV6 [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP41212 (Uniprot)
NextProtP41212  [Medical]
With graphics : InterProP41212
Splice isoforms : SwissVarP41212 (Swissvar)
Domaine pattern : Prosite (Expaxy)ETS_DOMAIN_1 (PS00345)    ETS_DOMAIN_2 (PS00346)    ETS_DOMAIN_3 (PS50061)    PNT (PS51433)   
Domains : Interpro (EBI)Ets_dom    Pointed_dom    SAM/pointed    WHTH_DNA-bd_dom   
Related proteins : CluSTrP41212
Domain families : Pfam (Sanger)Ets (PF00178)    SAM_PNT (PF02198)   
Domain families : Pfam (NCBI)pfam00178    pfam02198   
Domain families : Smart (EMBL)ETS (SM00413)  SAM_PNT (SM00251)  
DMDM Disease mutations2120
Blocks (Seattle)P41212
PDB (SRS)1JI7    1LKY    2DAO    2QAR    2QB0    2QB1   
PDB (PDBSum)1JI7    1LKY    2DAO    2QAR    2QB0    2QB1   
PDB (IMB)1JI7    1LKY    2DAO    2QAR    2QB0    2QB1   
PDB (RSDB)1JI7    1LKY    2DAO    2QAR    2QB0    2QB1   
Human Protein AtlasENSG00000139083
Peptide AtlasP41212
HPRD15976
IPIIPI00013159   IPI00969219   IPI01011903   IPI01010984   
Protein Interaction databases
DIP (DOE-UCLA)P41212
IntAct (EBI)P41212
FunCoupENSG00000139083
BioGRIDETV6
InParanoidP41212
Interologous Interaction database P41212
IntegromeDBETV6
STRING (EMBL)ETV6
Ontologies - Pathways
Ontology : AmiGOsequence-specific DNA binding transcription factor activity  protein binding  nucleus  transcription, DNA-templated  protein domain specific binding  cell differentiation  sequence-specific DNA binding  
Ontology : EGO-EBIsequence-specific DNA binding transcription factor activity  protein binding  nucleus  transcription, DNA-templated  protein domain specific binding  cell differentiation  sequence-specific DNA binding  
Pathways : KEGGDorso-ventral axis formation    Transcriptional misregulation in cancer   
REACTOMEETV6
Protein Interaction DatabaseETV6
Wikipedia pathwaysETV6
Gene fusion - rearrangments
Rearrangement : COSMICETV6 [12p13.2]  -  ITPR2 [12p12.1]
Rearrangement : COSMICETV6 [12p13.2]  -  JAK2 [9p24.1]
Rearrangement : COSMICETV6 [12p13.2]  -  NTRK3 [15q25.3]
Rearrangement : COSMICJAK2 [9p24.1]  -  ETV6 [12p13.2]
Rearrangement : COSMICNTRK3 [15q25.3]  -  ETV6 [12p13.2]
Rearrangement : TICdbABL1 [9q34.12]  -  ETV6 [12p13.2]
Rearrangement : TICdbABL2 [1q25.2]  -  ETV6 [12p13.2]
Rearrangement : TICdbACSL6 [5q31.1]  -  ETV6 [12p13.2]
Rearrangement : TICdbARNT [1q21.3]  -  ETV6 [12p13.2]
Rearrangement : TICdbBAZ2A [12q13.3]  -  ETV6 [12p13.2]
Rearrangement : TICdbCDX2 [13q12.2]  -  ETV6 [12p13.2]
Rearrangement : TICdbCHIC2 [4q12]  -  ETV6 [12p13.2]
Rearrangement : TICdbETV6 [12p13.2]  -  ABL1 [9q34.12]
Rearrangement : TICdbETV6 [12p13.2]  -  ABL2 [1q25.2]
Rearrangement : TICdbETV6 [12p13.2]  -  ACSL6 [5q31.1]
Rearrangement : TICdbETV6 [12p13.2]  -  ARNT [1q21.3]
Rearrangement : TICdbETV6 [12p13.2]  -  BAZ2A [12q13.3]
Rearrangement : TICdbETV6 [12p13.2]  -  CDX2 [13q12.2]
Rearrangement : TICdbETV6 [12p13.2]  -  CHIC2 [4q12]
Rearrangement : TICdbETV6 [12p13.2]  -  ETV6 [12p13.2]
Rearrangement : TICdbETV6 [12p13.2]  -  ETV6 [12p13.2]
Rearrangement : TICdbETV6 [12p13.2]  -  FGFR3 [4p16.3]
Rearrangement : TICdbETV6 [12p13.2]  -  FLT3 [13q12.2]
Rearrangement : TICdbETV6 [12p13.2]  -  GOT1 [10q24.2]
Rearrangement : TICdbETV6 [12p13.2]  -  ITPR2 [12p12.1]
Rearrangement : TICdbETV6 [12p13.2]  -  JAK2 [9p24.1]
Rearrangement : TICdbETV6 [12p13.2]  -  LYN [8q12.1]
Rearrangement : TICdbETV6 [12p13.2]  -  MDS2 [1p36.11]
Rearrangement : TICdbETV6 [12p13.2]  -  MECOM [3q26.2]
Rearrangement : TICdbETV6 [12p13.2]  -  MN1 [22q12.1]
Rearrangement : TICdbETV6 [12p13.2]  -  MNX1 [7q36.3]
Rearrangement : TICdbETV6 [12p13.2]  -  NKAIN2 [6q22.31]
Rearrangement : TICdbETV6 [12p13.2]  -  NTRK3 [15q25.3]
Rearrangement : TICdbETV6 [12p13.2]  -  PAX5 [9p13.2]
Rearrangement : TICdbETV6 [12p13.2]  -  PDGFRA [4q12]
Rearrangement : TICdbETV6 [12p13.2]  -  PDGFRB [5q32]
Rearrangement : TICdbETV6 [12p13.2]  -  PER1 [17p13.1]
Rearrangement : TICdbETV6 [12p13.2]  -  PRDM16 [1p36.32]
Rearrangement : TICdbETV6 [12p13.2]  -  RUNX1 [21q22.12]
Rearrangement : TICdbETV6 [12p13.2]  -  SYK [9q22.2]
Rearrangement : TICdbFGFR3 [4p16.3]  -  ETV6 [12p13.2]
Rearrangement : TICdbFLT3 [13q12.2]  -  ETV6 [12p13.2]
Rearrangement : TICdbGOT1 [10q24.2]  -  ETV6 [12p13.2]
Rearrangement : TICdbITPR2 [12p12.1]  -  ETV6 [12p13.2]
Rearrangement : TICdbJAK2 [9p24.1]  -  ETV6 [12p13.2]
Rearrangement : TICdbLYN [8q12.1]  -  ETV6 [12p13.2]
Rearrangement : TICdbMDS2 [1p36.11]  -  ETV6 [12p13.2]
Rearrangement : TICdbMECOM [3q26.2]  -  ETV6 [12p13.2]
Rearrangement : TICdbMN1 [22q12.1]  -  ETV6 [12p13.2]
Rearrangement : TICdbMNX1 [7q36.3]  -  ETV6 [12p13.2]
Rearrangement : TICdbNKAIN2 [6q22.31]  -  ETV6 [12p13.2]
Rearrangement : TICdbNTRK3 [15q25.3]  -  ETV6 [12p13.2]
Rearrangement : TICdbPAX5 [9p13.2]  -  ETV6 [12p13.2]
Rearrangement : TICdbPDGFRA [4q12]  -  ETV6 [12p13.2]
Rearrangement : TICdbPDGFRB [5q32]  -  ETV6 [12p13.2]
Rearrangement : TICdbPER1 [17p13.1]  -  ETV6 [12p13.2]
Rearrangement : TICdbPRDM16 [1p36.32]  -  ETV6 [12p13.2]
Rearrangement : TICdbRUNX1 [21q22.12]  -  ETV6 [12p13.2]
Rearrangement : TICdbSYK [9q22.2]  -  ETV6 [12p13.2]
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)ETV6
SNP (GeneSNP Utah)ETV6
SNP : HGBaseETV6
Genetic variants : HAPMAPETV6
1000_GenomesETV6 
ICGC programENSG00000139083 
Cancer Gene: CensusETV6 
Somatic Mutations in Cancer : COSMICETV6 
CONAN: Copy Number AnalysisETV6 
Mutations and Diseases : HGMDETV6
OMIM131440    600618    601626   
GENETestsETV6
Disease Genetic AssociationETV6
Huge Navigator ETV6 [HugePedia]  ETV6 [HugeCancerGEM]
Genomic VariantsETV6  ETV6 [DGVbeta]
Exome VariantETV6
dbVarETV6
ClinVarETV6
snp3D : Map Gene to Disease2120
General knowledge
Homologs : HomoloGeneETV6
Homology/Alignments : Family Browser (UCSC)ETV6
Phylogenetic Trees/Animal Genes : TreeFamETV6
Chemical/Protein Interactions : CTD2120
Chemical/Pharm GKB GenePA27909
Clinical trialETV6
Cancer Resource (Charite)ENSG00000139083
Other databases
Probes
ProbeETV6 (TEL) (12p13.1) in normal cells (Bari)
Litterature
PubMed179 Pubmed reference(s) in Entrez
CoreMineETV6
iHOPETV6

Bibliography

t(5;12)(q31;p12). A clinical entity with features of both myeloid leukemia and chronic myelomonocytic leukemia.
Wessels JW, Fibbe WE, van der Keur D, Landegent JE, van der Plas DC, den Ottolander GJ, Roozendaal KJ, Beverstock GC
Cancer genetics and cytogenetics. 1993 ; 65 (1) : 7-11.
PMID 8431918
 
Fusion of the TEL gene on 12p13 to the AML1 gene on 21q22 in acute lymphoblastic leukemia.
Golub TR, Barker GF, Bohlander SK, Hiebert SW, Ward DC, Bray-Ward P, Morgan E, Raimondi SC, Rowley JD, Gilliland DG
Proceedings of the National Academy of Sciences of the United States of America. 1995 ; 92 (11) : 4917-4921.
PMID 7761424
 
Fusion of TEL, the ETS-variant gene 6 (ETV6), to the receptor-associated kinase JAK2 as a result of t(9;12) in a lymphoid and t(9;15;12) in a myeloid leukemia.
Peeters P, Raynaud SD, Cools J, Wlodarska I, Grosgeorge J, Philip P, Monpoux F, Van Rompaey L, Baens M, Van den Berghe H, Marynen P
Blood. 1997 ; 90 (7) : 2535-2540.
PMID 9326218
 
Fusion of ETV6 to MDS1/EVI1 as a result of t(3;12)(q26;p13) in myeloproliferative disorders.
Peeters P, Wlodarska I, Baens M, Criel A, Selleslag D, Hagemeijer A, Van den Berghe H, Marynen P
Cancer research. 1997 ; 57 (4) : 564-569.
PMID 9044825
 
A t(6;12)(q23;p13) results in the fusion of ETV6 to a novel gene, STL, in a B-cell ALL cell line.
Suto Y, Sato Y, Smith SD, Rowley JD, Bohlander SK
Genes, chromosomes & cancer. 1997 ; 18 (4) : 254-268.
PMID 9087565
 
Fusion of ETV6 to the caudal-related homeobox gene CDX2 in acute myeloid leukemia with the t(12;13)(p13;q12).
Chase A, Reiter A, Burci L, Cazzaniga G, Biondi A, Pickard J, Roberts IA, Goldman JM, Cross NC
Blood. 1999 ; 93 (3) : 1025-1031.
PMID 9920852
 
Fusion of a novel gene, BTL, to ETV6 in acute myeloid leukemias with a t(4;12)(q11-q12;p13).
Cools J, Bilhou-Nabera C, Wlodarska I, Cabrol C, Talmant P, Bernard P, Hagemeijer A, Marynen P
Blood. 1999 ; 94 (5) : 1820-1824.
PMID 10477709
 
Fusion of TEL/ETV6 to a novel ACS2 in myelodysplastic syndrome and acute myelogenous leukemia with t(5;12)(q31;p13).
Yagasaki F, Jinnai I, Yoshida S, Yokoyama Y, Matsuda A, Kusumoto S, Kobayashi H, Terasaki H, Ohyashiki K, Asou N, Murohashi I, Bessho M, Hirashima K
Genes, chromosomes & cancer. 1999 ; 26 (3) : 192-202.
PMID 10502316
 
The MN1-TEL fusion protein, encoded by the translocation (12;22)(p13;q11) in myeloid leukemia, is a transcription factor with transforming activity.
Buijs A, van Rompaey L, Molijn AC, Davis JN, Vertegaal AC, Potter MD, Adams C, van Baal S, Zwarthoff EC, Roussel MF, Grosveld GC
Molecular and cellular biology. 2000 ; 20 (24) : 9281-9293.
PMID 11094079
 
A new ETV6/TEL partner gene, ARG (ABL-related gene or ABL2), identified in an AML-M3 cell line with a t(1;12)(q25;p13) translocation.
Iijima Y, Ito T, Oikawa T, Eguchi M, Eguchi-Ishimae M, Kamada N, Kishi K, Asano S, Sakaki Y, Sato Y
Blood. 2000 ; 95 (6) : 2126-2131.
PMID 10706884
 
The t(1;12)(q21;p13) translocation of human acute myeloblastic leukemia results in a TEL-ARNT fusion.
Salomon-Nguyen F, Della-Valle V, Mauchauffe M, Busson-Le Coniat M, Ghysdael J, Berger R, Bernard OA
Proceedings of the National Academy of Sciences of the United States of America. 2000 ; 97 (12) : 6757-6762.
PMID 10829078
 
Fusion of the homeobox gene HLXB9 and the ETV6 gene in infant acute myeloid leukemias with the t(7;12)(q36;p13).
Beverloo HB, Panagopoulos I, Isaksson M, van Wering E, van Drunen E, de Klein A, Johansson B, Slater R
Cancer research. 2001 ; 61 (14) : 5374-5377.
PMID 11454678
 
The paired box domain gene PAX5 is fused to ETV6/TEL in an acute lymphoblastic leukemia case.
Cazzaniga G, Daniotti M, Tosi S, Giudici G, Aloisi A, Pogliani E, Kearney L, Biondi A
Cancer research. 2001 ; 61 (12) : 4666-4670.
PMID 11406533
 
Fusion of ETV6 to fibroblast growth factor receptor 3 in peripheral T-cell lymphoma with a t(4;12)(p16;p13) chromosomal translocation.
Yagasaki F, Wakao D, Yokoyama Y, Uchida Y, Murohashi I, Kayano H, Taniwaki M, Matsuda A, Bessho M
Cancer research. 2001 ; 61 (23) : 8371-8374.
PMID 11731410
 
Chronic myelocytic leukemia with eosinophilia, t(9;12)(q34;p13), and ETV6-ABL gene rearrangement: case report and review of the literature.
Keung YK, Beaty M, Steward W, Jackle B, Pettnati M
Cancer genetics and cytogenetics. 2002 ; 138 (2) : 139-142.
PMID 12505259
 
A novel gene, MDS2, is fused to ETV6/TEL in a t(1;12)(p36.1;p13) in a patient with myelodysplastic syndrome.
Odero MD, Vizmanos JL, Romˆ°n JP, Lahortiga I, Panizo C, Calasanz MJ, Zeleznik-Le NJ, Rowley JD, Novo FJ
Genes, chromosomes & cancer. 2002 ; 35 (1) : 11-19.
PMID 12203785
 
Expression of the ETV6-NTRK3 gene fusion as a primary event in human secretory breast carcinoma.
Tognon C, Knezevich SR, Huntsman D, Roskelley CD, Melnyk N, Mathers JA, Becker L, Carneiro F, MacPherson N, Horsman D, Poremba C, Sorensen PH
Cancer cell. 2002 ; 2 (5) : 367-376.
PMID 12450792
 
A novel cryptic translocation t(12;17)(p13;p12-p13) in a secondary acute myeloid leukemia results in a fusion of the ETV6 gene and the antisense strand of the PER1 gene.
Penas EM, Cools J, Algenstaedt P, Hinz K, Seeger D, Schafhausen P, Schilling G, Marynen P, Hossfeld DK, Dierlamm J
Genes, chromosomes & cancer. 2003 ; 37 (1) : 79-83.
PMID 12661008
 
Identification of a novel fusion gene, TTL, fused to ETV6 in acute lymphoblastic leukemia with t(12;13)(p13;q14), and its implication in leukemogenesis.
Qiao Y, Ogawa S, Hangaishi A, Yuji K, Izutsu K, Kunisato A, Imai Y, Wang L, Hosoya N, Nannya Y, Sato Y, Maki K, Mitani K, Hirai H
Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2003 ; 17 (6) : 1112-1120.
PMID 12764377
 
Pediatric malignancies provide unique cancer therapy targets.
Uren A, Toretsky JA
Current opinion in pediatrics. 2005 ; 17 (1) : 14-19.
PMID 15659957
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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Contributor(s)

Written12-1999Serge Pierrick Romana
Service de Cytogenetique (Unite de Cytogenetique Moleculaire), Hopital Necker-Enfants-Malades, 149, rue de Sevres, 75015 Paris, France
Updated06-2005Stevan Knezevich

Citation

This paper should be referenced as such :
Romana S . ETV6 (ETS variant gene 6 (TEL oncogene)). Atlas Genet Cytogenet Oncol Haematol. December 1999 .
Knezevich S . ETV6 (ETS variant gene 6 (TEL oncogene)). Atlas Genet Cytogenet Oncol Haematol. June 2005 .
URL : http://AtlasGeneticsOncology.org/Genes/ETV6ID38.html

The various updated versions of this paper are referenced and archived by INIST as such :
http://documents.irevues.inist.fr/bitstream/2042/37554/1/12-1999-ETV6ID38.pdf   [ Bibliographic record ]
http://documents.irevues.inist.fr/bitstream/2042/38233/1/06-2005-ETV6ID38.pdf   [ Bibliographic record ]

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indexed on : Fri Apr 18 17:23:39 CEST 2014

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