ins(12;8)(p13;q11q21) ETV6/LYN
2015-02-01 Jean-Loup Huret Affiliation1.Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
Clinics and Pathology
Disease
Myeloproliferative disease (primary myelofibrosis).
Epidemiology
Only one case to date, a 21-year old male patient (Tanaka et al., 2010).
Prognosis
The patient died 11 months after diagnosis.
Genes Involved and Proteins
Gene name
LYN (LYN proto-oncogene, Src family tyrosine kinase)
Location
8q12.1
Protein description
512 amino acids. LYN contains from N-term to C-Term an SH3 domain (aa 63-123), a SH2 domain (aa 129-226) and a tyrisine kinase domain (aa 247-501). Non-receptor tyrosine kinase. LYN is mainly expressed in hematopoietic cells and is an important regulator of immune homeostasis.
Gene name
ETV6 (ets variant 6)
Location
12p13.2
Protein description
452 amino acids. The ETV6 protein contains from N-term to C-Term a HLH (helix-loop-helix, aa 40-124) domain (also referred to as the pointed or sterile alpha motif domain), responsible for hetero- and homodimerization, an internal domain, involved in the recruitment of a repression complex including NCOR1 (17p12), NCOR2 (12q24.31), SIN3A (15q24.2), and SIN3B (19p13.11), and an ETS domain (aa 339-420), responsible for sequence specific DNA-binding and protein-protein interaction (De Braekeleer et al., 2014).
Result of the Chromosomal Anomaly
Description
535 amino acids. The fusion protein is composed of the HLH domain and internal domain of ETV6 (336 N-term amino acids), fused to the tyrosine kinase domain of LYN (199 C-term amino acids).
Oncogenesis
ETV6-LYN is constitutively active: the PNT domain of ETV6 serves as an oligomerization domain and induces the constitutive activation of the tyrosine kinase domain from LYN through autophosphorylation; it directly activates STAT5A (17q21.2) and STAT5B (17q21.2) by phosphorylation, promotes the formation of proliferative colonies, and induces myeloproliferative neoplasms with myelofibrosis (Takeda et al., 2011).
Highly cited references
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 21492125 | 2011 | Direct activation of STAT5 by ETV6-LYN fusion protein promotes induction of myeloproliferative neoplasm with myelofibrosis. | 38 |
| 27058227 | 2016 | Myeloproliferative neoplasm with eosinophilia and T-lymphoblastic lymphoma with ETV6-LYN gene fusion. | 15 |
| 29153093 | 2017 | Next-generation sequencing and molecular cytogenetic characterization of ETV6-LYN fusion due to chromosomes 1, 8 and 12 rearrangement in acute myeloid leukemia. | 0 |
| 39704842 | 2025 | Whole exome sequencing analysis of a patient with myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions with ETV6::LYN fusion gene. | 0 |
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 21492125 | 2011 | Direct activation of STAT5 by ETV6-LYN fusion protein promotes induction of myeloproliferative neoplasm with myelofibrosis. | Takeda Y et al |
| 19710703 | 2010 | Identification of a novel TEL-Lyn fusion gene in primary myelofibrosis. | Tanaka H et al |
Summary
Fusion gene
ETV6/LYN ETV6 (12p13.2) LYN (8q12.1) TIC
Mesh
1
Citation
Jean-Loup Huret
ins(12;8)(p13;q11q21) ETV6/LYN
Atlas Genet Cytogenet Oncol Haematol. 2015-02-01
Online version: http://atlasgeneticsoncology.org/haematological/1535/ins(12;8)(p13;q11q21)-etv6-lyn
