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

Written2019-02Tatiana Gindina
R.M. Gorbacheva Memorial Institute of Children Oncology Hematology and Transplantation at First Pavlov Saint-Petersburg State Medical University, Saint-Petersburg, Russia /

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

Keywords chromosome 6; chromosome 12; acute lymphoblastic leukemia; acute myeloid leukemia; ETV6; FRK

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ICD-Topo C420,C421,C424
ICD-Morpho 9811/3 B lymphoblastic leukaemia/lymphoma, NOS
ICD-Morpho 9837/3 T lymphoblastic leukaemia/lymphoma
ICD-Morpho 9823/3 Chronic lymphocytic leukaemia /small lymphocytic lymphoma
ICD-Morpho 9874/3 AML with maturation
Atlas_Id 1322

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).
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).
# 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).


Additional anomalies Sole abnormality in 2 patients (1 ALL, 1 AML). Additional chromosome anomalies were observed in 6/8 patients. In early pre B-ALL t(6;12)(q21;p13) was associated in combination with extra chromosome 16 in 2 patients, and a complex karyotype in 2 cases (Hayashi et al., 1990; Raimondi et al., 1997). In small lymphocytic lymphoma, t(6;12)(q21;p13) is part of a complex karyotype.

Genes involved and Proteins

Gene NameETV6 (ets variant 6)
Location 12p13.2
Protein 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 NameFRK (Fyn-related Src family tyrosine kinase)
Location 6q22.1
Protein 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

Hybrid gene
  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.
Fusion Protein
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).

To be noted

Additional cases are needed to delineate the epidemiology of this rare entity:
you are welcome to submit a paper to our new Case Report section.


Nonrandom chromosome abnormalities in lymphoma.
Bloomfield CD, Arthur DC, Frizzera G, Levine EG, Peterson BA, Gajl-Peczalska KJ.
Cancer Research. 1983;43(6):2975-84.
PMID 6850608
The prognostic significance of deletion of the long arm of chromosome 20 in myelod disorders.
Campbell LJ, Garson OM.
Leukemia. 1994;8(1):67-71
PMID 8289501
Abnormalities of the long arm of chromosome 6 in childhood acute lymphoblastic leukemia.
Hayashi Y, Raimondi SC, Look AT, Behm FG, Kitchingman GR, Pui CH, Rivera GK, Williams DL.
Blood. 1990;76(8):1626-30.
PMID 2207332
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, Qiao Y, Hangaishi A, Wang L, Nannya Y, Sanada M, Kurokawa M, Chiba S, Hirai H, Ogawa S.
Genes Chromosomes Cancer. 2005;42(3):269-79
PMID 15611931
Chromosome and immunophenotypic patterns in T cell acute lymphoblastic leukemia and lymphoblastic lymphoma.
Kaneko Y, Frizzera G, Shikaro T, Kobayashi H, Maseki N, Sakurai M.
Leukemia. 1989;3(12):886-92.
PMID 2586183
Cytogenetic features of childhood acute lymphoblastic leukemia. A concordance study and a Pediatric Oncology Group study.
Katz JA, Tayloor LD, Carroll A, Elder FF, Mahoney DH.
Cancer Genet Cytogenet. 1991;55(2):249-56.
PMID 1933828
12p abnormalities and the TEL gene (ETV6) in childhood acute lymphoblastic leukemia.
Raimondi SC, Shurtleff SA, Downing JR, Rubnitz J, Mathew S, Hancock M, Pui CH, Rivera GK, Grosveld GC, Behm FG.
Blood. 1997;90(11):4559-66.
PMID 9373267


This paper should be referenced as such :
Gindina T
t(6;12)(q22;p13) ETV6/FRK;
Atlas Genet Cytogenet Oncol Haematol. in press
On line version :

Translocations implicated (Data extracted from papers in the Atlas)

 t(6;12)(q22;p13) ETV6/FRK

External links

Mitelman databaset(6;12)(q22;p13) [Case List]    t(6;12)(q22;p13) [Transloc-MCList] ETV6/FRK [Fusion-MCList]
arrayMap (UZH-SIB Zurich)Morph ( 9811/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMap (UZH-SIB Zurich)Morph ( 9837/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMap (UZH-SIB Zurich)Morph ( 9823/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMap (UZH-SIB Zurich)Morph ( 9874/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
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