From Compendium of Cancer Genome Aberrations
Jump to navigation Jump to search

Primary Author(s)*

Brian Davis PhD


"E26 transformation-specific variant 6"; "E-twenty-six variant 6"; ETS Variant 6; "Translocation-ETS-Leukemia"; TEL; THC5; TEL/ABL

Genomic Location

Cytoband: 12p13.2

Genomic Coordinates:



Cancer Category/Type

This ETV6 gene, either as a translocation partner with dozens of partner genes or having simple substitution mutations, is found at a low level in many cancers (see COSMIC); it is more prominent as a fusion protein in a number of hematological malignancies [1,2,see OMIM].

--- Myeloid Neoplasms with Germline ETV6 Mutation

--- B Lymphoblastic Leukaemia/Lymphoma with t(12;21)(p13;q22); TEL-AML1 (ETV6-RUNX1) Positive The t(12;21)(p13;q22) resulting in ETV6-RUNX1 fusion has been found in 25% of childhood B-cell acute lymphoblastic leukemia (B-ALL), but are much less common in adult B-ALL (only 2%) [2,5]. The fusion protein produced by the translocation confers a dominant negative effect on the normal RUNX1 protein, resulting in transcriptional activation become transcriptional repression [1,2]. The t(12;21) confers a favorable prognosis with cures seen in >90% of childhood B-ALL [1].

This translocation is a recurrent but rare finding in patients with acute myeloid leukemia [7], and a poor response to therapy has been reported.

ETV6 fused with PDGFRB has been found in patients with CMML [6].

  • Chronic Eosinophilic Leukemia (CEL)

The ETV6-PDGFRA fusion gene has been found in patients with chronic eosinophilic leukaemia (CEL), and these patients responded to low-dose imatinib [1].

Gene Overview

The ETV6 gene encodes one of 29 proteins in the ETS family of transcription factors ("ETS" is from "E26 transformation-specific" or "E-twenty-six"). The Etvs6 protein contains two functional domains: a N-terminal pointed (PNT) that is involved in protein-protein interactions with itself and other proteins, and a C-terminal, helix-loop-helix, DNA-binding domain (the ETS domain). Normally, the Etv6 protein acts as a transcriptional repressor and tumor supressor [2]. Familial genetic studies have shown that the protein is required for hematopoiesis and hematologic and other malignancies [3,4]. This gene is known to be involved in a large number of chromosomal rearrangements (over 30 fusion partners) associated with leukemia and congenital fibrosarcoma (adapted from NCBI Gene description). In most translocations, the N-terminal PNT domain of ETV6 is fused to a partner gene and acts as an aggregator for other proteins for a variety of effects, including transcriptional repression (eg, EVT6-RUNX1) [1,2] and constitutively activated tyrosine kinases (eg, ETV6-PDGFRB) [1].

Common Alteration Types

A large number of simple substitution mutations have been found spread throughout ETV6 in a large number of human malignancies at relatively low percentages (see COSMIC and see Cancer Index).

ETV6 has also been identified as a fusion partner in at least 30 chromosomal translocations and is frequently deleted either with or without the remaining allele being involved in a translocation [3, Atlas of Genetics and Cytogenetics in Oncology and Haematology, OMIM]. Some of these fusions include:


- ETV6/MN1











Copy Number Loss Copy Number Gain LOH Loss-of-Function Mutation Gain-of-Function Mutation Translocation/Fusion

Internal Pages

Myeloid Neoplasms with Germline ETV6 Mutation

Acute Lymphocytic Leukemia (ALL)

Chronic Myelomonocytic Leukemia (CMML)

B Lymphoblastic Leukaemia/Lymphoma with t(12;21)(p13;q22); TEL-AML1 (ETV6-RUNX1) Positive

Acute Myeloid Leukemia with t(4;12)(q12;p13),CHIC2-ETV6

External Links

ETV6 by Atlas of Genetics and Cytogenetics in Oncology and Haematology - detailed gene information

ETV6 by COSMIC - sequence information, expression, catalogue of mutations

ETV6 by St. Jude ProteinPaint mutational landscape and matched expression data.

ETV6 by Precision Medicine Knowledgebase (Weill Cornell) - manually vetted interpretations of variants and CNVs

ETV6 by Cancer Index - gene, pathway, publication information matched to cancer type

ETV6 by OncoKB - mutational landscape, mutation effect, variant classification

ETV6 by My Cancer Genome - brief gene overview

ETV6 by UniProt - protein and molecular structure and function

ETV6 by Pfam - gene and protein structure and function information

ETV6 by GeneCards - general gene information and summaries

ETV6 by NCBI Gene - general gene information and summaries

ETV6 by OMIM - compendium of human genes and genetic phenotypes

ETV6 by LOVD(3) - Leiden Open Variation Database

ETV6 by TICdb - database of Translocation breakpoints In Cancer


1. Arber DA, et al., (2017). Acute myeloid leukaemia with recurrent genetic abnormalities, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. Revised 4th Edition. IARC Press: Lyon, France.

2. Schafer ES, et al., (2015). Molecular genetics of acute lymphoblastic leukemia in the molecular basis of cancer, 4th edition. Mendelsohn, J, Howley, PM, Israel, MA, Gray, JW, Thompson, CB. Editors. Elsevier Press: Philadelphia, USA, p395-406.

3. Hock H, et al., (2017). ETV6 in hematopoiesis and leukemia predisposition. Semin Hematol 54:98-104, PMID 28637624. DOI: 10.1053/j.seminhematol.2017.04.005.

4. Zhang MY, et al., (2015). Germline ETV6 mutations in familial thrombocytopenia and hematologic malignancy, Nature Genet 47:180–185, PMID 25581430. DOI: 10.1038/ng.3177.

5. Golub TR, et al., (1995). Fusion of the TEL gene on 12p13 to the AML1 gene on 21q22 in acute lymphoblastic leukemia. Proc Natl Acad Sci U S A 92(11):4917-4921, PMID 7761424.

6. Apperley JF, et al., (2002). Response to imatinib mesylate in patients with chronic myeloproliferative diseases with rearrangements of the platelet-derived growth factor receptor beta. N Engl J Med. 347(7):481-487, PMID 12181402.

7. Cools J, et al., (1999). Fusion of a novel gene, BTL, to ETV6 in acute myeloid leukemias with a t(4;12)(q11-q21;p13). Blood 94(5):1820-1824, PMID 10477709.


*Primary authors will typically be those that initially create and complete the content of a page. If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage). Additional global feedback or concerns are also welcome.