ETV6
Primary Author(s)*
Brian Davis PhD
Synonyms
"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:
chr12:11,802,788-12,048,336(GRCh37/hg19)
chr12:11,649,854-11,895,402(GRCh38/hg38)
Cancer Category/Type
This ETV6 gene, either as a translocation partner with dozens of partner genes or as simple substitution mutations is found at a low level in many cancers see COSMIC), but is more prominent as a fusion protein in a number of hematological malignancies [1,2,see OMIM].
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]. 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].
ETV6 fused with PDGFRB has been found in patients with CMML (Golub et al. (1994) and chronic myeloproliferative disorder Apperley et al. (2002). acute lymphocytic leukemia ETV6/RUNX1 Golub et al. (1995). 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
ETV6 has been identified as a fusion partner in at least 30 chromosomal translocations [3, Atlas of Genetics and Cytogenetics in Oncology and Haematology, OMIM]. 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 constitutive activated tyrosine kinases (eg, ETV6-PDGFRB) [1]. A large number of simple substitution mutations have been found spread throughout the gene and these have been found in a large number of human malignancies at relatively low percentages (see COSMIC and see Cancer Index).
ETV6/PDGFRB fusion
ETV6/MN1 fusion
ETV6/AML1 fusion
ETV6/ARNT fusion
ETV6/MDS2 fusion
ETV6/ABL2 fusion
ETV6/PER1 fusion
ETV6/NTRK3 fusion
ETV6/ACS2 fusion
ETV6/BTL fusion
ETV6/JAK2 fusion
ETV6/RUNX1 fusion
| Copy Number Loss | Copy Number Gain | LOH | Loss-of-Function Mutation | Gain-of-Function Mutation | Translocation/Fusion |
|---|---|---|---|---|---|
| X | X | X | X | X |
Internal Pages
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
References
1 .Arber DA, et al., (2008). Acute myeloid leukaemia with recurrent genetic abnormalities, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW, Editors. IARC Press: Lyon, France, p117-118.
2. Schafer, E.S. . 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, M.Y et al. (2015). Germline ETV6 mutations in familial thrombocytopenia and hematologic malignancy, Nature Genet. 47: 180–185. PMID 25581430 DOI: 10.1038/ng.3177
Notes
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