Changes

==Synonyms==

==Synonyms==

ETS Variant 6; TEL; THC5; TEL/ABL

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

==Genomic Location==

==Genomic Location==

'''Genomic Coordinates:'''  

'''Genomic Coordinates:'''  

chr12:11,802,788-12,048,336(GRCh37/hg19)

chr12:11,802,788-12,048,336(GRCh37/hg19)

==Cancer Category/Type==

==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.  

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/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].

 

chronic myeloproliferative disorder ETV6/PDGFRB Apperley et al. (2002)  

* '''[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]'''

16% of the childhood B-lineage acute lymphoblastic leukemia Romana et al. (1995)

* '''[http://www.ccga.io/index.php/HAEM5:Chronic_myelomonocytic_leukaemia Chronic Myelomonocytic Leukemia (CMML)]''''

==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 Protein Etvs6 contains two functional domains: a N-terminal pointed (PNT) domain that is involved in protein-protein interactions with itself and other proteins, and a C-terminal DNA-binding domain. The protein is required for hematopoiesis and maintenance of the developing vascular network. This gene is known to be involved in a large number of chromosomal rearrangements associated with leukemia and congenital fibrosarcoma. ([https://www.ncbi.nlm.nih.gov/gene/2120 addapted form NCBI Gene description]).

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==

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/RUNX1

ETV6/RUNX1 fusion

{| 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==

'''[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]'''

EXAMPLE [[Germline Cancer Predisposition Genes]]

==External Links==

==External Links==

==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.

 

 

 

 

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.

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.

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 ==