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:
Put your text here
chr12:11,802,788-12,048,336(GRCh37/hg19)
chr12:11,649,854-11,895,402(GRCh38/hg38)
Cancer Category/Type
'chronic myelomonocytic leukemia'
t(5;12)(q33;p13) translocation ETV6-PDGFRB (Golub et al. (1994) translocation consisting of the 154 N terminal residues of ETV6 linked to the transmembrane and tyrosine kinase domains of the PDGFRB on chromosome 5q33.
chronic myeloproliferative disorder ETV6/PDGFRB Apperley et al. (2002)
acute lymphocytic leukemia ETV6/RUNX1 Golub et al. (1995)
B-cell acute lymphoblastic leukemia (B-ALL)
t(12;21)(p13;q22); 25% of childhood B-cell acute lymphoblastic leukemia (B-ALL) bear an ETV6-RUNX1 translocation, but are much less common (on;y 2%) in adult B-cell acute lymphoblastic leukemia (B-ALL) [2]. The ETV6-RUNX1 trans - location produces a fusion protein that confers a dominant negative effect on the normal RUNX1 protein function (Transcriptional activation become transcriptional repression) (1, 2]. The ETV6-RUNXT1 translocation confers a favourable prognosis with cures seen in >90% of childhood B-ALL [1].
chronic eosinophilic leukaemia (CEL)
ETV6-PDGFRA fusion gene, both with the haematological features of CEL, responded to low-dose imatinib [1]
t(5;12)(q31~33;p12) with formation of an ETV6-PDGFRB fusion gene In cases with t(5;12), and in the variant translocations, there is synthesis of an aberrant, constitutively activated tyrosine kinase. The haematological features are most often those of CMML (usually with eosinophilia) but some patients have been characterized as atypical chronic myeloid leukaemias (aCML) (usually with eosinophilia), CEL and MPN with eosinophilia
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 associated with leukemia and congenital fibrosarcoma. (addapted 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], constitutive Activated tyrosine kinases (eg, ETV6-PDGFRB) [1],
Transcriptional repressor; binds to the DNA sequence 5-CCGGAAGT-3. Plays a role in hematopoiesis and malignant transformation.
Common Alteration Types
ETV6 has been identified as a fusion partner in at least 30 chromosomal translocation genes [3, Atlas of Genetics and Cytogenetics in Oncology and Haematology].
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 t(12;21)(p13;q22); ETV6-RUNX1
| Copy Number Loss | Copy Number Gain | LOH | Loss-of-Function Mutation | Gain-of-Function Mutation | Translocation/Fusion |
|---|---|---|---|---|---|
| EXAMPLE: X | EXAMPLE: X | EXAMPLE: X | EXAMPLE: X | EXAMPLE: X | EXAMPLE: X |
Internal Pages
Put your text here
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
*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.