t(6;12)(q22;p13) ETV6/FRK
2019-02-01 Tatiana Gindina Affiliation1.R.M. Gorbacheva Memorial Institute of Children Oncology Hematology and Transplantation at First Pavlov Saint-Petersburg State Medical University, Saint-Petersburg, Russia / [email protected]
Abstract
Review on t(6;12)(q21;p13), with data on the genes involved
Clinics and Pathology
Disease
Translocation t(6;12)(q21;p13) is a rare abnormality, it occurs in both myeloid and lymphoid disorders including AML, ALL, and NHL.
Acute lymphoblastic leukemia (ALL) was diagnosed in 6 pediatric patients, 4 of them were with early pre-B ALL (Raimondi et al., 1997; Hayashi et al., 1990), one patient with T-ALL (Kaneko et al., 1989).
Acute myeloid leukemia (AML): there were 2 adult patients (Hosoya et al., 2005; Campbell et al., 1994).
Small lymphocytic lymphoma was diagnosed in 1 patient (Bloomfield et al., 1983).
Acute lymphoblastic leukemia (ALL) was diagnosed in 6 pediatric patients, 4 of them were with early pre-B ALL (Raimondi et al., 1997; Hayashi et al., 1990), one patient with T-ALL (Kaneko et al., 1989).
Acute myeloid leukemia (AML): there were 2 adult patients (Hosoya et al., 2005; Campbell et al., 1994).
Small lymphocytic lymphoma was diagnosed in 1 patient (Bloomfield et al., 1983).
Epidemiology
The t(6;12)(q21;p13) is a rare reciprocal translocation. Male predominance (Male : Female 3,5 : 1).
Table 1. Reported cases with t(6;12)(q21;p13).
Table 1. Reported cases with t(6;12)(q21;p13).
| # | Age, gender | Diseasenbsp; | Karyotype | Author |
| 1 | 7, M | Early pre-B ALL | 48,XY,t(6;12)(q21;p13),+16,+add(19)(p13) | Raimondi et al, 1997 |
| 2 | 5,5, M | Early pre-B ALL | 46,XY,inv(12)(p13q22),add(21)(q22)/46,idem,t(6;12)(q21;p13)/46,XY,t(6;12),inv(12) | Raimondi et al, 1997 |
| 3 | ?, M | ALL | 46,XY,t(6;12)(q21;pl3)/46,XY | Katz et al, 1991 |
| 4 | ?, M | Early pre-B ALL | 48,XY.+16,+der(19)t(19;?)(p13;?),t(6:12)(q21;p13)/48XY,+16,+der(19),d e1(12)(p12),t(6;12) | Hayashi et al., 1990 |
| 5 | ?, M | Early pre-B ALL | 46,XY,inv(12)(p13q22).-21,+der(21)t(21;?)(q22;?)/46,XY,t(6;12)(q21:p13),inv(12),-21,+der(21)/46,XY,t(6;12),inv(12) | Hayashi et al., 1990 |
| 6 | 10, F | T-cell ALL | 46,XX,t(6;12)(q21;p13),t(7;14)(p15;q32) | Kaneko et al., 1989 |
| 7 | 69, M | Small Lymphocytic Lymphoma | 43-44,XY,-4,-7,-9,-11,-13,-17,t(1;14)(p32;q32),t(6;12)(q21;p13),+der(7)t(7;?)(p22;?)+der(13)t(13;?)(q34;?),+der(17)t(17;17)(p13;?),+20 | Bloomfield 1983 |
| 8 | 69, F | AML | 46,XX,t(6;12)(q21;p13) | Hosoya et al., 2005 |
| 9 | 55, M | AML with maturation (FAB type M2) | 54,XY,t(6;12)(q21;p13),+8,+9,+10,+11,+13,+14,add(17)(p11),+20,+del(20)(q11),+21 | Campbell et al., 1994 |
Prognosis
Survival in ALL and AML patients was 40, 106+ and 5 months respectively (Raimondi et al, 1997; Hosoya et al, 2005).
Genes Involved and Proteins
Gene name
ETV6 (ets variant 6)
Location
12p13.2
Protein description
ETV6 encodes an ETS family transcription factor. ETV6 protein contains two functional domains: a N-terminal pointed (PNT) domain that is involved in protein-protein interactions with other proteins, and a C-terminal DNA-binding domain. Gene knockout studies suggest that it is required for hematopoiesis and maintenance of the developing vascular network. ETV6 is known to be involved in a large number of chromosomal abnormalities associated with leukemia and inborn fibrosarcoma.
Gene name
FRK (Fyn-related Src family tyrosine kinase)
Location
6q22.1
Protein description
FRK belongs to a family of SRC kinases. SRC is the prototype for a family of genes that encode non-receptor tyrosine kinases implicated in a variety of cellular processes. The wild type FRK is expressed primarily in epithelial tissues, but also weakly in the various hematopoietic cell lines. However, its functions or downstream signaling pathways remain largely unknown, especially in hematopoietic systems. The only known candidate endogenous downstream component of FRK is the SH2-domain adaptor protein SHB (Hosoya et al., 2005).
Result of the Chromosomal Anomaly
Schematic representation of wild-type ETV6, FRK, and the fusion transcript ETV6/FRK. The breakpoints are indicated by vertical arrows.
Description
In the resultant ETV6/FRK fusion protein, the entire PNT oligomerization domain of ETV6 and the kinase domain of FRK are fused in frame.
Oncogenesis
It has been shown that ETV6/FRK is an oncoprotein with dual functions: deregulated tyrosine kinase activity and a dominant-negative modulation of transcriptional repression by ETV6. Because wild-type ETV6 appears to have tumor-suppressive activity, its suppression by ETV6/ FRK also could contribute to oncogenesis (Hosoya et al., 2005).
Highly cited references
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 37601849 | 2023 | Leukaemic cells expressing ETV6::FRK are sensitive to dasatinib in vivo. | 9 |
| 15611931 | 2005 | Identification of a SRC-like tyrosine kinase gene, FRK, fused with ETV6 in a patient with acute myelogenous leukemia carrying a t(6;12)(q21;p13) translocation. | 0 |
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 6850608 | 1983 | Nonrandom chromosome abnormalities in lymphoma. | Bloomfield CD et al |
| 8289501 | 1994 | The prognostic significance of deletion of the long arm of chromosome 20 in myeloid disorders. | Campbell LJ et al |
| 2207332 | 1990 | Abnormalities of the long arm of chromosome 6 in childhood acute lymphoblastic leukemia. | Hayashi Y et al |
| 15611931 | 2005 | Identification of a SRC-like tyrosine kinase gene, FRK, fused with ETV6 in a patient with acute myelogenous leukemia carrying a t(6;12)(q21;p13) translocation. | Hosoya N et al |
| 2586183 | 1989 | Chromosomal and immunophenotypic patterns in T cell acute lymphoblastic leukemia (T ALL) and lymphoblastic lymphoma (LBL). | Kaneko Y et al |
| 1933828 | 1991 | Cytogenetic features of childhood acute lymphoblastic leukemia. A concordance study and a Pediatric Oncology Group study. | Katz JA et al |
| 9373267 | 1997 | 12p abnormalities and the TEL gene (ETV6) in childhood acute lymphoblastic leukemia. | Raimondi SC et al |
Summary
Fusion gene
ETV6/FRK
Citation
Tatiana Gindina
t(6;12)(q22;p13) ETV6/FRK
Atlas Genet Cytogenet Oncol Haematol. 2019-02-01
Online version: http://atlasgeneticsoncology.org/haematological/1322/teaching-explorer/submit-meetings/gene-explorer/cancer-prone-explorer/
