Changes

==Cancer Category/Type==

==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 [https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=etv6 see COSMIC]), but is more prominent as a fusion protein in a number of hematological malignancies [1,2,[http://www.omim.org/entry/600618 see OMIM]].

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/Acute_lymphoblastic_leukaemia_(ALL) Acute Lymphocytic Leukemia (ALL)]'''

* '''[http://www.ccga.io/index.php/Acute_lymphoblastic_leukaemia_(ALL) Acute Lymphocytic Leukemia (ALL)]'''

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].

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/Chronic_Myelomonocytic_Leukemia_(CMML) Chronic Myelomonocytic Leukemia (CMML)]''''

* Chronic Eosinophilic Leukemia (CEL)

''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].

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==

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]).   

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 [3, [http://atlasgeneticsoncology.org/Genes/ETV6ID38.html Atlas of Genetics and Cytogenetics in Oncology and Haematology], [http://www.omim.org/entry/600618 OMIM]]. These fusions include:  

''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/PDGFRB

! 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  

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==Internal Pages==

==Internal Pages==

==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.

 

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.

 

 

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.

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.

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.

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

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.

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

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 ==