ETV6 (ets variant 6)

2014-03-01 Etienne De Braekeleer , Nathalie Douet-Guilbert , Marc De Braekeleer Affiliation

Cytogenetics Laboratory, Faculty of Medicine, University of Brest, France

Identity

HGNC

ETV6

LOCATION

12p13.2

IMAGE

LEGEND

ETV6 (12p13.2) in normal cells: clone dJ852F10 - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.

LEGEND

ETV6 (ets variant 6) Hybridization with Vysis ETV6 break apart rearrangement probe (Abbott Molecular, US) showing the gene on 12p13.2 (red-green or a fused yellow signal) - Courtesy Adriana Zamecnikova.

LOCUSID

2120

ALIAS

TEL,TEL/ABL,THC5

FUSION GENES

Show Gene Fusions

Abstract

The ETV6 gene located at band 12p13 encodes a protein containing two major domains, the HLH (helix-loop-helix) domain, encoded by exons 3 and 4, and the ETS domain, encoded by exons 6 through 8, with in between the internal domain encoded by exon 5. ETV6 is a strong transcriptional repressor, acting through its HLH and internal domains. Five potential mechanisms of ETV6-mediated carcinogenesis have been identified: constitutive activation of the kinase activity of the partner protein, modification of the original functions of a transcription factor, loss of function of the fusion gene, affecting ETV6 and the partner gene, activation of a proto-oncogene in the vicinity of a chromosomal translocation and dominant negative effect of the fusion protein over transcriptional repression mediated by wild-type ETV6. Thirty-three ETV6 partner genes have been identified.

DNA/RNA

Schematic diagram of the ETV6 gene showing the 8 exons. Exon 1b is an alternative exon located in intron 2. Reprinted from Leukemia Research, vol 36, De Braekeleer E et al. ETV6 fusion genes in hematological malignancies: A review. Pages 945-961, 2012. With permission from Elsevier.

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. There are two start codons, one (exon 1a starting at codon 1) located at the beginning of the gene and another alternative (exon 1b starting at codon 43) upstream of exon 3.

Transcription

Transcription is from telomere to centromere; there are three species of transcripts : 2400 kb, 4300 kb and 6200 kb; the gene encodes for a 1356 kb cDNA.

Proteins

Schematic diagram of the ETV6 protein showing the major domains. Reprinted from Leukemia Research, vol 36, De Braekeleer E et al. ETV6 fusion genes in hematological malignancies: A review. Pages 945-961, 2012. With permission from Elsevier.

Description

The ETV6 protein is a 452 amino acid polypeptide that shares homology at the 5 and 3 ends with other ETS family members. ETS proteins form one of the largest families of signal-dependent transcriptional regulators, mediating cell proliferation, differentiation and tumorigenesis. The ETV6 protein contains two major domains, the HLH (helix-loop-helix) and ETS domains. The HLH domain, also referred to as the pointed or sterile alpha motif domain, is encoded by exons 3 and 4 and is responsible for hetero- and homodimerization with other ETV6 proteins and possibly other ets family members. The ETS domain, encoded by exons 6 through 8, is responsible for sequence specific DNA-binding and protein-protein interaction. A central domain, called internal domain, is encoded by exon 5 and is involved in the recruitment of a repression complex including N-Cor, mSin3 and SMRT.

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

The ETV6 protein plays a crucial role in the embryonic development and hematopoietic regulation. ETV6 is essential for normal development and is specifically required for maintaining blood vessel integrity within the developing yolk sac and survival of different cell types in the developing embryo. ETV6 is essential for the establishment of hematopoiesis of all lineages in the bone marrow.
ETV6 is a strong transcriptional repressor. Repression is mediated by the HLH domain and the internal domain. Repression by the HLH domain is mediated through interaction with the HLH domain of L3MBTL1, a member of the polycomb group of chromatin-associated proteins, that can maintain long term repression of genes through a histone deacetylase-independent mechanism. Repression by the internal domain is mediated through interaction with corepressors such as N-Cor, mSin3 and SMRT, which in turn can recruit histone deacetylases.

Mutations

Note

ETV6 is implicated in leukemia, myelodysplastic syndromes and sarcoma.
Deletions: ETV6 is frequently deleted in hematological malignancies. The deletion of the normal (untranslocated) ETV6 allele in the presence of a translocation affecting ETV6 is quite frequent, notably in patients with ETV6-RUNX1, ETV6-NTRK3, ETV6-ABL1, ETV6-ACSL6 and ETV6-STL fusion. Deletion of an ETV6 allele has also been observed in the absence of rearrangement of the second allele.

Implicated in

Entity name

t(1;12)(p36;p13) MDS2/ETV6

Disease

One CML with t(9;22) (no molecular analysis) and one refractory anemia with excess of blasts in transformation.

Fusion protein

Truncated ETV6 protein lacking critical functional domains and suggesting a loss of function of ETV6.

Oncogenesis

Loss of function of ETV6? Expression of RPL11, centromeric to MDS2 (63.5 kb) much higher in the patient than in controls.

Entity name

t(1;12)(q21;p13) ARNT/ETV6

Disease

One AML-M2 and one T-cell acute lymphoblastic leukemia.

Hybrid gene

The ETV6-ARNT transcript contains the first 4 exons of ETV6 fused in frame with exon 1 or 2 of ARNT.

Fusion protein

The ETV6-ARNT protein contains the oligomerization domain of ETV6 and almost all of the ARNT protein, including its major domains.

Oncogenesis

Given the presence of the oligomerization domain of ETV6 in the ETV6-ARNT protein, it is expected that the HLH domain of ETV6 convert ARNT from a transcriptional activator into a repressor. Furthermore, the ETV6-ARNT fusion protein retaining the HLH domain of ETV6 could interact with the other ETV6 protein.

Entity name

t(1;12)(q25;p13) ABL2/ETV6

Disease

AML-M3, AML-M4, T-cell ALL, B-cell ALL.

Hybrid gene

Breakpoint in intron 5 of ETV6 in all three cases.

Fusion protein

Fusion protein contains the HLH oligomerization domain of ETV6 and the SH2, SH3, and protein tyrosine kinase domains of ABL2.

Oncogenesis

Constitutive activation of the kinase activity of ABL2.

Entity name

t(3;12)(q26;p13) MDS1-EVI1 (MECOM)/ETV6

Note

Rare, but recurrent, chromosomal aberration (more than 30 cases). Few patients studied on a molecular level.

Disease

Myeloproliferative disorders, myelodysplastic syndromes and acute myelogenous leukemia.

Hybrid gene

Two different mechanisms for generating the fusion gene.
First mechanism: in-frame chimeric transcript consisting of the first two exons of ETV6 fused to MDS1 sequences, which in turn is fused to the second exon of the EVI1 gene.
Second mechanism: direct fusion between ETV6 and EVI1, in which case an out-of-frame fusion between exon 2 of ETV6 and exon 2 of EVI1 is generated but the open reading frame of EVI1 is not disrupted.

Fusion protein

In both fusion types, ETV6 contributes no known functional domain to the predicted chimeric protein.

Oncogenesis

Oncogenic potential of the translocation could be the result of the ETV6 promoter driving the transcription of EVI1, resulting in activation of the transcription factor EVI1, which is not normally expressed in hematopoietic cells.

Entity name

t(4;12) (p16;p13) FGFR3/ETV6

Disease

Peripheral T-cell lymphoma

Hybrid gene

Fusion of exon 5 of ETV6 to exon 10 of FGFR3.

Fusion protein

Protein consists of the HLH domain of ETV6 and the tyrosine kinase domain of FGFR3.

Oncogenesis

Constitutive activation of the kinase activity of FGFR3.

Entity name

t(4;12)(q11;p13) CHIC2 (BTL)/ETV6

Note

Rare but recurrent chromosomal abnormality. Ten cases with molecular analysis showed a CHIC2/ETV6 fusion gene.

Disease

AML (FAB type M0, M1, M2, therapy-related), RAEB.

Hybrid gene

At least two different mechanisms.
First mechanism: In-frame fusion between CHIC2 exons 1-3 and exons 2-8 of the ETV6 gene.
Second mechanism: Breakpoints located in introns 1 and 2 of ETV6 but outside the CHIC2 gene, with no detectable CHIC2-ETV6 fusion gene.

Fusion protein

Fusion protein contains both the HLH and ETS domains of ETV6 but no specific domain of CHIC2.

Oncogenesis

Ectopic expression of GSX2 detected in all cases studied, with or without the CHIC2-ETV6 fusion. GSX2 contains a homeobox domain very similar to the homeobox of the clustered HOX genes, which are involved in both normal and abnormal hematopoiesis. Overexpression of GSX2, but not CHIC2-ETV6 has transforming properties.

Entity name

t(5;12)(q31;p13) ACSL6/ETV6

Note

Recurrent translocation occurring in various myeloid malignancies, often associated with eosinophilia. Only seven cases with molecular analysis.

Disease

Myelodysplastic syndrome (RAEB), AML, AEL, atypical CML, Polycythemia Vera.

Hybrid gene

Different fusion genes are generated in four patients:
- in-frame fusion of exon 1 of ETV6 to the 3UTR of ACSL6
- out-of-frame fusion of exon 1 of ETV6 to exon 1 of ACSL6
- in-frame fusion of exon 1 of ETV6 to almost the complete ACSL6 (breakpoint at the 5 end of the ACSL6 gene).

Oncogenesis

Given the absence of a common in-frame fusion gene generated by the t(5;12)(q31;p13) and the heterogeneity in the localization of the ACSL6 breakpoints, no common fusion protein can explain the pathogenic character of the translocation. IL3, located near the breakpoint at 5q31, is ectopically expressed in the leukemic cells, leading to a proliferative defect.

Entity name

t(5;12)(q33;p13) PDGFRB/ETV6

Note

Recurrent chromosomal abnormality (dozens of cases).

Disease

Myeloproliferative/myelodysplastic syndrome (usually referred as atypical Philadelphia-negative CML and CMML) with eosinophilia.

Hybrid gene

Exon 4 of the ETV6 gene is generally fused in-frame to exon 11 of the PDGFRB gene.
Two cases showing a different fusion gene with the ETV6 breakpoint in intron 7.

Fusion protein

Protein includes the HLH domain of ETV6 and the tyrosine kinase domain of PDGFRB.
In both cases showing a different fusion gene, the fusion protein retains the internal domain of ETV6 which has the ability to bind to corepressors and induce the transcription-repressive activity of ETV6.

Oncogenesis

Constitutive activation of the kinase activity of PDGFRB.
In both cases showing a different fusion gene, it is likely that the fusion protein acts differently from that observed in the other cases.

Entity name

t(6;12)(q23;p13) STL/ETV6

Note

Only one case reported.

Disease

B-cell ALL.

Hybrid gene

Fusion gene only retains the first two exons of ETV6.

Fusion protein

Fusion protein contains no important domains (HLH or ETS) of ETV6.

Oncogenesis

It is likely that the truncated ETV6 contributes to leukemogenesis through ETV6 haploinsufficiency.

Entity name

t(7;12)(q36;p13) MNX1(HLXB9)/ETV6

Note

Recurrent translocation found in 20 to 30% of AML children less than 18 months of age. The 7q36 breakpoint heterogeneity suggests that this translocation does not lead to the formation of a unique fusion gene. Six cases with molecular analysis showing a MNX1/ETV6 fusion.

Disease

AML

Hybrid gene

5 MNX1-3 ETV6 resulting in a transcript in which MNX1 exon 1 is joined with ETV6 exon 3.

Fusion protein

Protein contains the HLH and ETS domains of ETV6 but not the homeobox domain of MNX1.

Oncogenesis

It is thought that the chimeric protein acts as an aberrant transcription factor, which could affect both MNX1 and ETV6 pathways of transcription modulation.

Entity name

dic(9;12)(p13;p13) PAX5/ETV6

Note

Nonrandom chromosome abnormality found in about 1% of childhood B-cell ALL.

Disease

ALL.

Hybrid gene

5PAX5-3ETV6 transcript with fusion of exon 4 of PAX5 to exon 3 of ETV6.

Fusion protein

The PAX5-ETV6 protein contains the "paired box" (DNA binding) domain of PAX5 fused to the HLH and ETS-binding domains of ETV6.

Oncogenesis

It is thought that the chimeric protein could act as an aberrant transcription factor, which could affect both PAX5 and ETV6 pathways of transcription modulation.

Entity name

t(9;12) (p24;p13) JAK2/ETV6

Note

Only six cases described with ETV6/JAK2 fusion.

Disease

Pre-B ALL, atypical CML, T-cell ALL.

Hybrid gene

Breakpoint variability: introns 4 and 5 of ETV6 and introns 12 and 17 of JAK2.

Fusion protein

Protein retains the HLH domain of ETV6 but different domains of JAK2 (complete JH2 and JH1 in one case, only part of JH2 in the other).

Oncogenesis

Constitutive activation of the kinase activity of JAK2.

Entity name

t(9;12)(q22;p13) SYK/ETV6

Note

Only two cases reported.

Disease

MDS.

Hybrid gene

Chimeric gene fuses the first 5 exons of ETV6 with SYK starting with exon 5.

Fusion protein

Fusion protein contains the HLH domain of ETV6 with part of the C-terminal SH2 and the complete protein kinase domain of SYK.

Oncogenesis

Constitutive activation of SYK kinase activity.

Entity name

t(9;12)(q34;p13) ABL1/ETV6

Note

26 cases described with different hemopathies but eosinophilia is a common feature.

Disease

Acute myeloblastic leukemia (AML), chronic myelogenous leukemia (CML), B-cell acute lymphocytic leukemia (ALL), T-cell ALL, MDS (RAEB), chronic myeloproliferative neoplasm, Philadelphia chromosome-negative CML.

Hybrid gene

Two ETV6-ABL1 transcripts are usually identified: one joining exon 5 of ETV6 to exon 2 of ABL1 and one joining ETV6 exon 4 to ABL1 exon 2.

Fusion protein

The protein retains all three SH domains, including the tyrosine kinase domain, of ABL1 and the HLH domain of ETV6.

Oncogenesis

Tyrosine kinase activation of ABL1.

Entity name

t(10;12)(q24;p13) GOT1/ETV6

Note

Two cases of MDS described.

Disease

MDS (RA and RAEB).

Hybrid gene

Transcript containing exon 2 to exon 9 of GOT1 and the first 2 or 3 exons of ETV6.

Fusion protein

Absence or truncation of the HLH domain of ETV6 in the protein.

Oncogenesis

Possibly inactivation of the wild type ETV6.

Entity name

t(12;13)(p13;q12) ETV6/CDX2

Note

The t(12;13)(p13;q12-14) is a rare, but recurrent, translocation reported in a range of malignant hemopathies. However, it is evident from FISH studies that they are heterogeneous at the molecular level.

Disease

CML in transformation, myelodysplastic syndrome (MDS), acute non lymphocytic leukemia (AML), B and T- ALL. A sole case with ETV6/CDX2 fusion in a AML-M1.

Hybrid gene

One in-frame fusion between exon 2 of ETV6 and exon 2 of CDX2; one fusion introducing an in-frame stop codon.

Fusion protein

ETV6 contributes no functional domain to the fusion protein.

Oncogenesis

It is likely that the ETV6 promoter drives the transcription and ectopic activation of CDX2, which has leukemogenesis properties.

Entity name

t(12;13)(p13;q14) ETV6/TTL [not annotated gene in HGNC]

Note

Identified in several cases of ALL and less frequently in acute or chronic myeloid malignancies.

Disease

A sole case with TTL/ETV6 fusion in a ALL.

Hybrid gene

ETV6/TTL fusion transcript: 3 TTL sequence introduces an in-frame stop codon after the end of ETV6 exon 1.
TTL-ETV6 transcript is a direct in-frame fusion between TTL exon 5 and ETV6 exon 2.

Fusion protein

No ETV6 functional domains in the ETV6/TTL protein; HLH and ETS domains conserved in TTL-ETV6 protein.

Oncogenesis

Chimeric protein could act as an aberrant transcription factor, affecting the ETV6 pathway of transcription modulation, or there could be a loss of function of ETV6 and/or TTL.

Entity name

t(12;15)(p13;q25) ETV6/NTRK3

Disease

Congenital Fibrosarcoma, Congenital Mesoblastic Nephroma (cellular and mixed variants), Secretory Ductal Carcinoma of Breast, rarely in AML (M0, M2) and chronic eosinophilia leukemia (1 case).

Hybrid gene

5 ETV6-3 NTRK3.

Fusion protein

Fusion protein retains the HLH domain of ETV6 and the protein tyrosine kinase (PTK) domain of NTRK3.

Oncogenesis

Constitutive active tyrosine kinase.

Entity name

t(12;17)(p13;p13) ETV6/PER1

Disease

Only one case of AML evolving from CMML.

Hybrid gene

Fusion between exon 1 of the ETV6 gene and exon 22 and part of intron 21 of PER1.

Fusion protein

No protein as PER1 has an antisense orientation.

Oncogenesis

It is proposed that PER1 inactivation or deregulated expression of genes located close to the breakpoint, such as HES7 or STK12, could contribute to leukemogenesis.

Entity name

t(12;21)(p13;q22) ETV6/RUNX1

Note

Most common structural chromosomal abnormality in pediatric common or B-cell acute lymphoblastic leukemia, accounting for about 20-25% of the cases.

Disease

Childhood B-cell (ALL).

Hybrid gene

Fusion of the 5 region of ETV6 (from exon 1 to 5) with almost the entire coding region of RUNX1.

Fusion protein

The fusion protein retains the HLH domain and the central repression domain of ETV6 as well as the RHD (Runt homology domain) and the transcription activation domain of RUNX1.

Oncogenesis

The ETV6-RUNX1 fusion protein retains the ability to bind the RUNX1 target sequences and functions as a histone deacetylase (HDAC)-dependent repressor, causing deregulation of the RUNX1 target genes. ETV6-RUNX1 is also likely to disrupt normal ETV6 functions through HLH-mediated heterodimerization.

Entity name

t(12;22)(p13;q11) MN1/ETV6

Note

Rare anomaly in myeloid hemopathies (6 cases with molecular analysis).

Disease

Myeloproliferative disorder, myelodysplastic syndrome, AML.

Hybrid gene

Two different types of MN1/ETV6 fusion (types I and II).

Fusion protein

Type I fusion protein contains almost the entire MN1 fused to ETV6 at a position N terminal to the HLH domain whereas type II fusion protein has only part of the HLH domain, making it nonfunctional. Both fusion types retain the ETS domain.

Oncogenesis

Could act as an altered transcription factor by activating ETV6-responsive transcription and/or inhibiting RAR-mediated transcription and/or being a dominant-negative suppressor of MN1.

Entity name

t(4;12)(q23;p13) ETV6/PDGFRA

Note

PDGFRA is a gene found to be fused with several partners in chronic eosinophilic leukemia.

Disease

Only one case of myeloproliferative neoplasm associated with hypereosinophilia and ETV6/PDGFRA fusion.

Hybrid gene

In-frame fusion gene between ETV6 exon 6 and PDGFRA exon 11.

Fusion protein

Protein retains most of ETV6, including the HLH domain and part of the ETS domain, fused to the WW-like domain and the kinase domain of PDGFRA.

Oncogenesis

Constitutive protein kinase activation.

Entity name

t(12;13)(p13;q12) ETV6/FLT3

Note

FLT3 is one of the most frequently mutated genes in hematological malignancies, being found in about 30% of AML patients and rarely in ALL patients.

Disease

Three cases of myeloproliferative neoplasm with hypereosinophilia associated with ETV6/FLT3 fusion.

Hybrid gene

In-frame fusion gene between ETV6 exon 4 or exon 5 and FLT3 exon 14.

Fusion protein

Protein retains the HLH domain of ETV6 and the tyrosine kinase domains of FLT3.

Oncogenesis

Constitutively tyrosine kinase activation.

Entity name

t(6;12)(q21;p13) ETV6/FRK

Disease

Only one case of AML-M4.

Hybrid gene

ETV6 exon 4 fused in frame to exon 3 of FRK.

Fusion protein

Chimeric protein composed of the HLH domain of ETV6 and most of the SH2 (likely to be nonfunctional) and the kinase domains of FRK.

Oncogenesis

Dual action of constitutively tyrosine kinase activation and dominant-negative effect on ETV6-mediated transcriptional repression.

Entity name

ins(12;8)(p13;q11q21) ETV6/LYN

Disease

Only one case of primary myelofibrosis associated with ETV6/LYN.

Hybrid gene

Chimeric gene consists of the 5 region of ETV6 (breakpoint in intron 5) and the 3 region of LYN.

Fusion protein

Protein retains the HLH domain of ETV6 and the tyrosine kinase domain of LYN.

Oncogenesis

Constitutively tyrosine kinase activation.

Entity name

inv(12)(p13q13) ETV6/PTPRR

Disease

Only one case of AML-M2 associated with ETV6/PTPRR.

Hybrid gene

ETV6 exon 4 is fused to exon 7 of the PTPRR; 10 isoforms through alternative splicing.

Fusion protein

A truncated ETV6 including the HLH domain but no functional domains of PTPRR due to frameshift and a chimeric ETV6-PTPRR protein that includes the HLH domain of ETV6 and the protein tyrosine phosphatase domain of PTPRR among others.

Oncogenesis

Dominant negative effect over transcriptional repression mediated by wild-type ETV6.

Entity name

t(8;12)(q13;p13) ETV6/NCOA2

Disease

Pediatric acute biphenotypic leukemia (6 cases with ETV6/NCOA2), adult T-ALL (1 case).

Hybrid gene

Two different in-frame fusions are known:
- one between ETV6 exon 5 and NCOA2 exon 14 (one case).

Fusion protein

Protein consists of the HLH domain of ETV6 and the CBP interaction and the AD2 (transactivation domain 2) acetyltransferase domains of NCOA2.

Oncogenesis

It is hypothesized that the ETV6-NCOA2 protein acts as a modulator of the transcriptional activity of CBP-dependent activators or can recruit CBP to ETV6 target genes resulting in their constitutive activation.

Entity name

Cryptic rearrangement shown by FISH between 12p13 and 12q24 ETV6/BAZ2A in a t(?1;12)(q42;p13)

Disease

Only one case of pre-B ALL.

Hybrid gene

Fusion of ETV6 and BAZ2A consisting of exons 1 and 2 of ETV6 and a sequence from intron 1 of BAZ2A.

Fusion protein

No chimeric protein expected to be produced, but, maybe, a truncated ETV6.

Oncogenesis

It is likely that the truncated ETV6 contributes to leukemogenesis through ETV6 haploinsufficiency.

Entity name

t(5;12;22)(q13;p13;q11) ETV6/FCHO2

Disease

Only one case of AML-M1.

Hybrid gene

Transcript consisting of ETV6 exons 1 and 2 with sequences of FCHO2.

Fusion protein

No chimeric protein expected to be produced (genes in opposite orientations following the translocation), but, maybe, a truncated ETV6.

Oncogenesis

It is likely that the truncated ETV6 contributes to leukemogenesis through ETV6 haploinsufficiency.

Entity name

t(12;14)(p13;q32) ETV6/IGH co-localization

Disease

One case of pediatric pre-B ALL.

Cytogenetics

Co-localization of both ETV6 and IGH signals by FISH (no molecular analysis).

Entity name

t(12;22)(p13;q12) ETV6/EMID1

Disease

Only one case of AML-M2.

Cytogenetics

Co-localization of both ETV6 and EMID1 signals by FISH (no molecular analysis).

Fusion protein

No chimeric protein expected to be produced (genes in opposite orientations following the translocation), but, maybe, a truncated ETV6.

Entity name

t(12;17)(p13;q21) ETV6/RARA

Disease

Only one case of myelofibrosis evolved in AML.

Cytogenetics

Co-localization of both ETV6 and RARA signals by FISH (no molecular analysis).

Fusion protein

No chimeric protein expected to be produced (genes in opposite orientations following the translocation), but, maybe, a truncated ETV6.

Entity name

t(5;12)(p13;p13) NIPBL/ETV6

Disease

Only one case of acute megakaryoblastic leukemia (AML-M7).

Cytogenetics

Co-localization of both ETV6 and NIPBL signals by FISH (no molecular analysis).

Breakpoints

Chromosomal distribution of the 33 ETV6 partners thus far identified.

Physical map of the breakpoint distribution in the ETV6 gene. Yellow boxes: receptor tyrosine kinase genes; orange boxes: non-receptor tyrosine kinase genes; red boxes: transcription factor genes; green boxes: homeobox genes; blue boxes: other genes. Reprinted from Leukemia Research, vol 36, De Braekeleer E. et al. ETV6 fusion genes in hematological malignancies: A review. Pages 945-961, 2012. With permission from Elsevier.

Bibliography

Pubmed ID	Last Year	Title	Authors

Other Information

Locus ID:

NCBI: 2120
MIM: 600618
HGNC: 3495
Ensembl: ENSG00000139083

Variants:

dbSNP: 2120
ClinVar: 2120
TCGA: ENSG00000139083
COSMIC: ETV6

RNA/Proteins

Gene ID	Transcript ID	Uniprot
ENSG00000139083	ENST00000266427	J3KN52
ENSG00000139083	ENST00000396373	P41212
ENSG00000139083	ENST00000396373	A0A0S2Z3C9
ENSG00000139083	ENST00000545027	H0YG25

Expression (GTEx)

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Pathways

Pathway	Source	External ID
Dorso-ventral axis formation	KEGG	ko04320
Dorso-ventral axis formation	KEGG	hsa04320
Transcriptional misregulation in cancer	KEGG	ko05202
Transcriptional misregulation in cancer	KEGG	hsa05202

Protein levels (Protein atlas)

Not detected

Low

Medium

High

PharmGKB

Entity ID	Name	Type	Evidence	Association	PK	PD	PMIDs
PA446155	Precursor Cell Lymphoblastic Leukemia-Lymphoma	Disease	MultilinkAnnotation	associated			26522332

References

Pubmed ID	Year	Title	Citations
12450792	2002	Expression of the ETV6-NTRK3 gene fusion as a primary event in human secretory breast carcinoma.	201
18202291	2008	Initiating and cancer-propagating cells in TEL-AML1-associated childhood leukemia.	115
19475667	2009	SNCA variants are associated with increased risk for multiple system atrophy.	110
19913121	2009	Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.	85
25581430	2015	Germline ETV6 mutations in familial thrombocytopenia and hematologic malignancy.	85
17015828	2006	TEL-AML1 transgenic zebrafish model of precursor B cell acute lymphoblastic leukemia.	68
22162831	2011	ETV6 mutations in early immature human T cell leukemias.	68
20379614	2010	Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.	62
25807284	2015	Germline mutations in ETV6 are associated with thrombocytopenia, red cell macrocytosis and predisposition to lymphoblastic leukemia.	62
24327398	2014	ETV6-NTRK3 is a common chromosomal rearrangement in radiation-associated thyroid cancer.	58

Citation

Etienne De Braekeleer ; Nathalie Douet-Guilbert ; Marc De Braekeleer

ETV6 (ets variant 6)

Atlas Genet Cytogenet Oncol Haematol. 2014-03-01

Online version: http://atlasgeneticsoncology.org/gene/38/meetings/cancer-prone-explorer/

Historical Card

2005-06-01 ETV6 (ets variant 6) by Stevan Knezevich Affiliation

BC Cancer Research Centre (BCCRC), Vancouver, British Columbia, Canada

1999-12-01 ETV6 (ets variant 6) by Serge Pierrick Romana Affiliation

Service de Cytogenetique (Unite de Cytogenetique Moleculaire), Hopital Necker-Enfants-Malades, 149, rue de Sevres, 75015 Paris, France