Changes

==Cancer Category/Type==

==Cancer Category/Type==

''[http://www.ccga.io/index.php/Chronic_Myelomonocytic_Leukemia_(CMML) 'chronic myelomonocytic leukemia]'''

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]].

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.

The translocation t(12;21)(p13;q22) ETV6-RUNX1 has been found in 25% of childhood B-cell acute lymphoblastic leukemia (B-ALL) , but are much less common (only 2%)  in adult B-cell acute lymphoblastic leukemia (B-ALL) [2].  The ETV6-RUNX1 trans -

 

 

 

 

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

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].

seen in >90% of childhood B-ALL [1].

chronic eosinophilic leukaemia (CEL)

ETV6 fused with PDGFRB has been found in patients with [http://www.ccga.io/index.php/Chronic_Myelomonocytic_Leukemia_(CMML) 'chronic myelomonocytic leukemia] (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]

ETV6-PDGFRA fusion gene, both with the haematological features of CEL, 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 associated with leukemia and congenital fibrosarcoma. ([https://www.ncbi.nlm.nih.gov/gene/2120 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],

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 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==

==Common Alteration Types==

ETV6 has been identified as a fusion partner in at least 30 chromosomal translocation genes [3, [http://atlasgeneticsoncology.org/Genes/ETV6ID38.html Atlas of Genetics and Cytogenetics in Oncology and Haematology]].   

ETV6 has been identified as a fusion partner in at least 30 chromosomal translocation genes [3, [http://atlasgeneticsoncology.org/Genes/ETV6ID38.html Atlas of Genetics and Cytogenetics in Oncology and Haematology], [http://www.omim.org/entry/600618 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 ([https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=etv6 see COSMIC and [http://www.cancerindex.org/geneweb/ETV6.htm Cancer Index]).   

ETV6/PDGFRB fusion

ETV6/PDGFRB fusion

ETV6/BTL fusion

ETV6/BTL fusion

ETV6/JAK2 fusion

ETV6/JAK2 fusion

ETV6/RUNX1 fusion t(12;21)(p13;q22); 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

|}

|}

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==Internal Pages==

==External Links==

==External Links==