t(6;12)(q22;p13) ETV6/FRK

2019-02-01   Tatiana Gindina 

1.R.M. Gorbacheva Memorial Institute of Children Oncology Hematology and Transplantation at First Pavlov Saint-Petersburg State Medical University, Saint-Petersburg, Russia / tatgindina@gmail.com


Review on t(6;12)(q21;p13), with data on the genes involved

Clinics and Pathology


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).


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).
# 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


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)
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)
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

Atlas Image
Schematic representation of wild-type ETV6, FRK, and the fusion transcript ETV6/FRK. The breakpoints are indicated by vertical arrows.


In the resultant ETV6/FRK fusion protein, the entire PNT oligomerization domain of ETV6 and the kinase domain of FRK are fused in frame.


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).


Pubmed IDLast YearTitleAuthors


Fusion gene



Tatiana Gindina

t(6;12)(q22;p13) ETV6/FRK

Atlas Genet Cytogenet Oncol Haematol. 2019-02-01

Online version: http://atlasgeneticsoncology.org/haematological/1322/t(6;12)(q22;p13)-etv6-frk