ETV6 (ETS variant gene 6 (TEL oncogene))

Identity

Other names	TEL (translocation ets leukemia)
Hugo	ETV6
Location	12p13.1
	ETV6 (12p13.1) in normal cells: clone dJ852F10 - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics. Laboratories willing to validate the probes are wellcome: contact M Rocchi

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
Hugo	ETV6
GDB	ETV6
Entrez_Gene	ETV6  2120  ets variant gene 6 (TEL oncogene)
	Cards
Atlas	ETV6ID38
GeneCards	ETV6
Ensembl	ETV6 [Search_View]   ENSG00000139083 [Gene_View]
Genatlas	ETV6
GeneLynx	ETV6
eGenome	ETV6
euGene	2120
	Genomic and cartography
GoldenPath	ETV6  -  12p13.1   chr12:11694055-11939592 +  12p13   [Description]    (hg18-Mar_2006)
Ensembl	ETV6 - 12p13 [CytoView]
NCBI	Mapview
OMIM	Disease map [OMIM]
HomoloGene	ETV6
	Gene and transcription
Genbank	AA205762 [ ENTREZ ]
Genbank	AA452592 [ ENTREZ ]
Genbank	AI660081 [ ENTREZ ]
Genbank	AK289441 [ ENTREZ ]
Genbank	AV722693 [ ENTREZ ]
RefSeq	NM_001987 [ SRS ]    NM_001987 [ ENTREZ ]
RefSeq	AC_000055 [ SRS ]    AC_000055 [ ENTREZ ]
RefSeq	NC_000012 [ SRS ]    NC_000012 [ ENTREZ ]
RefSeq	NT_009714 [ SRS ]    NT_009714 [ ENTREZ ]
RefSeq	NW_925328 [ SRS ]    NW_925328 [ ENTREZ ]
AceView	ETV6 AceView - NCBI
Unigene	Hs.504765 [ SRS ]    Hs.504765 [ NCBI ]     HS504765 [ spliceNest ]
Fast-db	2775 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	P41212 [ SRS]    P41212 [ EXPASY ]     P41212 [ INTERPRO ]
Prosite	PS00345 ETS_DOMAIN_1 [ SRS ]    PS00345 ETS_DOMAIN_1 [ Expasy ]
Prosite	PS00346 ETS_DOMAIN_2 [ SRS ]    PS00346 ETS_DOMAIN_2 [ Expasy ]
Prosite	PS50061 ETS_DOMAIN_3 [ SRS ]    PS50061 ETS_DOMAIN_3 [ Expasy ]
Interpro	IPR000418 Ets [ SRS ]    IPR000418 Ets [ EBI ]
Interpro	IPR003118 SAM_PNT [ SRS ]    IPR003118 SAM_PNT [ EBI ]
Interpro	IPR013761 SAM_type [ SRS ]    IPR013761 SAM_type [ EBI ]
Interpro	IPR011991 Wing_hlx_DNA_bd [ SRS ]    IPR011991 Wing_hlx_DNA_bd [ EBI ]
CluSTr	P41212
Pfam	PF00178 Ets [ SRS ]    PF00178 Ets [ Sanger ]    pfam00178 [ NCBI-CDD ]
Pfam	PF02198 SAM_PNT [ SRS ]    PF02198 SAM_PNT [ Sanger ]    pfam02198 [ NCBI-CDD ]
Smart	SM00413 ETS [EMBL]
Smart	SM00251 SAM_PNT [EMBL]
Blocks	P41212
PDB	1JI7 [ SRS ]    1JI7 [ PdbSum ],   1JI7 [ IMB ]   1JI7 [ RSDB ]
PDB	1LKY [ SRS ]    1LKY [ PdbSum ],   1LKY [ IMB ]   1LKY [ RSDB ]
PDB	2DAO [ SRS ]    2DAO [ PdbSum ],   2DAO [ IMB ]   2DAO [ RSDB ]
HPRD	15976
	Protein Interaction databases
DIP	P41212
IntAct	P41212
	Polymorphism : SNP, mutations, diseases
OMIM	131440;600618;601626    [ map ]
GENECLINICS	131440;600618;601626
SNP	ETV6 [dbSNP-NCBI]
SNP	NM_001987 [SNP-NCI]
SNP	ETV6 [GeneSNPs - Utah]  ETV6] [HGBASE - SRS]
HAPMAP	ETV6 [HAPMAP]
COSMIC	ETV6 [Somatic mutation (COSMIC-CGP-Sanger)]
TICdb	ETV6 [Translocation breakpoints In Cancer]
HGMD	ETV6
	General knowledge
Family Browser	ETV6 [UCSC Family Browser]
SOURCE	NM_001987
SMD	Hs.504765
SAGE	Hs.504765
GO	transcription factor activity [Amigo]  transcription factor activity
GO	protein binding [Amigo]  protein binding
GO	nucleus [Amigo]  nucleus
GO	transcription [Amigo]  transcription
GO	regulation of transcription, DNA-dependent [Amigo]  regulation of transcription, DNA-dependent
GO	sequence-specific DNA binding [Amigo]  sequence-specific DNA binding
KEGG	Dorso-ventral axis formation
PubGene	ETV6
TreeFam	ETV6
CTD	2120 [Comparative ToxicoGenomics Database]
	Other databases
	Probes
Probe	ETV6 (TEL) (12p13.1) in normal cells (Bari)
Probe	ETV6 Related clones (RZPD - Berlin)
	PubMed
PubMed	80 Pubmed reference(s) in LocusLink

Bibliography

t(5;12)(q31;p12). A clinical entity with features of both myeloid leukemia and chronic myelomonocytic leukemia.

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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

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Contributor(s)

Written	12-1999	Serge Pierrick Romana
		Service de Cytogenetique (Unite de Cytogenetique Moleculaire), Hopital Necker-Enfants-Malades, 149, rue de Sevres, 75015 Paris, France

Citation

This paper should be referenced as such :

Romana S . ETV6 (ETS variant gene 6 (TEL oncogene)). Atlas Genet Cytogenet Oncol Haematol. December 1999 . URL : http://AtlasGeneticsOncology.org/Genes/ETV6ID38.html

Knezevich S . ETV6 (ETS variant gene 6 (TEL oncogene)). Atlas Genet Cytogenet Oncol Haematol. . URL : http://AtlasGeneticsOncology.org/Genes/ETV6ID38.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Wed Jul 2 08:23:26 2008