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==Synonyms==
==Synonyms==
"E26 transformation-specific variant 6"; "E-twenty-six variant 6"; ETS Variant 6; "Translocation-ETS-Leukemia"; TEL; THC5; TEL/ABL
==Genomic Location==
==Genomic Location==
'''Cytoband:''' Put your text here. EXAMPLE: 17p13.1
'''Cytoband:''' 12p13.2
'''Genomic Coordinates:'''
'''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 having simple substitution mutations, is found at a low level in many cancers ([https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=etv6 see COSMIC]); it is more prominent as a fusion protein in a number of hematological malignancies [1,2,[http://www.omim.org/entry/600618 see OMIM]].
*'''[http://www.ccga.io/index.php/Myeloid_Neoplasms_with_Germline_Predisposition Myeloid Neoplasms with Germline Predisposition]'''
--- '''[http://www.ccga.io/index.php/HAEM4:Myeloid_Neoplasms_with_Germline_ETV6_Mutation Myeloid Neoplasms with Germline ETV6 Mutation]'''
* '''[http://www.ccga.io/index.php/Acute_lymphoblastic_leukaemia_(ALL) Acute Lymphocytic Leukemia (ALL)]'''
--- '''[http://www.ccga.io/index.php/B_lymphoblastic_leukaemia/lymphoma_with_t(12;21)(p13;q22);_TEL-AML1_(ETV6-RUNX1)_positive 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].
* '''[http://www.ccga.io/index.php/Acute_myeloid_leukemia_with_t(4;12)(q12;p13),_CHIC2-ETV6 Acute Myeloid Leukemia with t(4;12)(q12;p13),CHIC2-ETV6]'''
This translocation is a recurrent but rare finding in patients with acute myeloid leukemia [7], and a poor response to therapy has been reported.
* '''[http://www.ccga.io/index.php/HAEM5:Chronic_myelomonocytic_leukaemia Chronic Myelomonocytic Leukemia (CMML)]''''
''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==
==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 ([https://www.ncbi.nlm.nih.gov/gene/2120 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==
==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 ([https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=etv6 see COSMIC] and [http://www.cancerindex.org/geneweb/ETV6.htm 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, [http://atlasgeneticsoncology.org/Genes/ETV6ID38.html Atlas of Genetics and Cytogenetics in Oncology and Haematology], [http://www.omim.org/entry/600618 OMIM]]. Some of these fusions include:
- ETV6/PDGFRB
- ETV6/MN1
- ETV6/AML1
- ETV6/ARNT
- ETV6/MDS2
- ETV6/ABL2
- ETV6/PER1
- ETV6/NTRK3
- ETV6/ACS2
- ETV6/BTL
- ETV6/JAK2
- ETV6/RUNX1
{| class="wikitable sortable"
{| class="wikitable sortable"
! Copy Number Loss !! Copy Number Gain !! LOH !! Loss-of-Function Mutation !! Gain-of-Function Mutation !! Translocation/Fusion
! 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
| X || X || X || X || X || X
|}
|}
==Internal Pages==
==Internal Pages==
'''[[HAEM4:Myeloid Neoplasms with Germline ETV6 Mutation]]'''
'''[http://www.ccga.io/index.php/Acute_lymphoblastic_leukaemia_(ALL) Acute Lymphocytic Leukemia (ALL)]'''
'''[http://www.ccga.io/index.php/HAEM5:Chronic_myelomonocytic_leukaemia Chronic Myelomonocytic Leukemia (CMML)]'''
'''[http://www.ccga.io/index.php/B_lymphoblastic_leukaemia/lymphoma_with_t(12;21)(p13;q22);_TEL-AML1_(ETV6-RUNX1)_positive B Lymphoblastic Leukaemia/Lymphoma with t(12;21)(p13;q22); TEL-AML1 (ETV6-RUNX1) Positive]'''
'''[http://www.ccga.io/index.php/Acute_myeloid_leukemia_with_t(4;12)(q12;p13),_CHIC2-ETV6 Acute Myeloid Leukemia with t(4;12)(q12;p13),CHIC2-ETV6]'''
==External Links==
'''[http://atlasgeneticsoncology.org/Genes/ETV6ID38.html ''ETV6'' by Atlas of Genetics and Cytogenetics in Oncology and Haematology]''' - detailed gene information
'''[http://atlasgeneticsoncology.org/Genes/ETV6ID38.html ''ETV6'' by Atlas of Genetics and Cytogenetics in Oncology and Haematology]''' - detailed gene information
'''[https://pmkb.weill.cornell.edu/search?utf8=%E2%9C%93&search=etv6 ''ETV6'' by Precision Medicine Knowledgebase (Weill Cornell)]''' - manually vetted interpretations of variants and CNVs
'''[https://pmkb.weill.cornell.edu/search?utf8=%E2%9C%93&search=etv6 ''ETV6'' by Precision Medicine Knowledgebase (Weill Cornell)]''' - manually vetted interpretations of variants and CNVs
'''[http://www.cancerindex.org/geneweb/etv6.htm ''ETV6'' by Cancer Index]''' - gene, pathway, publication information matched to cancer type
'''[http://www.cancerindex.org/geneweb/ETV6.htm ''ETV6'' by Cancer Index]''' - gene, pathway, publication information matched to cancer type
'''[http://oncokb.org/#/gene/etv6 ''ETV6'' by OncoKB]''' - mutational landscape, mutation effect, variant classification
'''[http://oncokb.org/#/gene/etv6 ''ETV6'' by OncoKB]''' - mutational landscape, mutation effect, variant classification
==References==
==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.
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.
== Notes ==
== Notes ==