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t(10;12)(q24;p13) ETV6/GOT1

Written2008-09Iwona Wlodarska
Center for Human Genetics, Catholic University Leuven, Leuven, Belgium

(Note : for Links provided by Atlas : click)


ICD-Morpho 9975/3 Chronic myelogenous leukaemia, BCR-ABL1 positive; Myeloproliferative neoplasm, unclassifiable; Myelodysplastic/myeloproliferative neoplasm, unclassifiable
ICD-Morpho 9989/3 Myelodysplastic syndrome, unclassifiable
Atlas_Id 1451
  Scheme of t(10;12)(q24;p13)

Clinics and Pathology

Disease Myeloid disorders:
  • Myelodysplastic syndrome ( MDS ) type refractory anemia ( RA ) (Wlodarska et al., 1995) and refractory anemia with excess blasts ( RAEB ) (Struski et al., 2008).
  • Philadelphia chromosome positive chronic myeloid leukemia ( CML ) in transformation (Aguiar et al., 1997).
  • Etiology Only 3 cases so far; 77-year old male (MDS-RA) and 71-year old female (MDS-RAEB). No data available on a case of CML.
    Prognosis Unknown so far.


    Cytogenetics Molecular FISH demonstrated ETV6 involvement in both MDS cases. In a case of CML, the 12p13 breakpoint was mapped between ETV6 (11.9 Mb) and GDID4 (15 Mb). In addition, FISH detected a cryptic deletion of CDKN1B (12.7 Mb) associated with this translocation.
      FISH with cosmids specific for the 5' end (c179A6) and the 3' end (c148B6) of ETV6 in a case of MDS-RA (Wlodarska et al., 1995).
    Additional anomalies The translocation was found as a sole aberration in a case of MDS-RA, in a subclone with del(5)(q13q34) in a case of MDS-RAEB, and was accompanying t(9;22)(q34;q11) in a case of CML.
    Variants The ETV6-involving t(10;12)(q24;p13) was recognized as the first variant of t(5;12)(q33;p13) targeting ETV6 and PDGFRB (Wlodarska et al., 1995) (Golub et al., 1994). So far, at least 24 ETV6-associated fusion transcripts have been identified in human malignancies.

    Genes involved and Proteins

    Gene NameETV6 (ets variant 6)
    Location 12p13.2
    Dna / Rna ETV6 encodes an ets (E-26 transforming specific) family transcription factor. Three transcripts have been described: ETV6-202 (8 exons; length 5.974 bps; 452 amino acids), ETV6-203 (10 exons; length 5.697 bps; 451 amino acids) and ETV6-201 (5 exons; length 1836 bps; 61 amino acids). Transcription is from telomere to centromere.
    Protein Two functional domains have been indentified: a N-terminal Helix-Loop-Helix domain (or pointed (PNT) or Sterile Alpha Motif (SAM)domain) responsible for hetero- and homodimerization with itself and possibly other proteins, and a C-terminal ETS domain responsible for a specific DNA binding. HLH domain is encoded by exons 3 and 4, and ETS domain by exons 6-8. As a transcription regulator, ETV6 is localized in the nucleus.
    Experimental data suggest that ETV6 is required for hematopoiesis and maintenance of the developing vascular network.
    Gene NameGOT1 (glutamic-oxaloacetic transaminase 1)
    Location 10q24.2
    Dna / Rna 9 exons; transcript of 10942 bps. Transcription is from telomere to centromere.
    Protein GOT1 encodes for a cytosolic form of an ubiquitous pyridoxal phosphate-dependent enzyme. The enzyme plays an important role in amino acid metabolism and in the urea and tricarboxylic acid cycles. The GOT1 protein is 413-amino acid long and its predicted molecular weight is 46 kDA.

    Result of the chromosomal anomaly

    Hybrid gene
    Note Molecular consequences of the seemingly looking t(10;12)(q24;p13) found in MDS and CML seem to be different.
    Description Both MDS cases showed the ETV6-GOT1 transcript formed by an in frame fusion between the first two exons of ETV6 and exon 2 to exon 9 of GOT1 (MDS-RA), or by fusion of exon 3 of ETV6 with exon 2 of GOT1 (MDS-RAEB). In both cases additional not-in frame fusions involving ETV6 and sequences telomeric to GOT1 have been identified.
    The t(10;12) found in a case of CML in transformation does not involve ETV6; the 12p13 breakpoint was mapped between ETV6 and GDID4. Whether this translocation results in an in frame fusion or is a bystander event associated with the deletion of CDKN1B detected in this case is unknown.
    Fusion Protein
    Description The molecular consequences of the ETV6-GOT1 fusion remain unclear. It has been postulated that the fusion protein, only lacking a short N-terminal part of GOT1, can still form heterodimers with wild type GOT1, thereby acting as a dominant negative form, resulting in a reduction of GOT1 enzymatic activity in dysplastic cells. In addition, the translocation could also deregulate the expression of genes located upstream of GOT1 (e.g. c10orf139, found to be overexpressed in the MDS-RA case) or leads to inactivation of ETV6.

    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.


    Characterization of a t(10;12)(q24;p13) in a case of CML in transformation.
    Aguiar RC, Chase A, Oscier DG, Carapeti M, Goldman JM, Cross NC.
    Genes Chromosomes Cancer. 1997 Dec;20(4):408-11.
    PMID 9408758
    Fusion of PDGF receptor beta to a novel ets-like gene, tel, in chronic myelomonocytic leukemia with t(5;12) chromosomal translocation.
    Golub TR, Barker GF, Lovett M, Gilliland DG.
    Cell. 1994 Apr 22;77(2):307-16.
    PMID 8168137
    Fusion of ETV6 to GOT1 in a case with myelodysplastic syndrome and t(10;12)(q24;p13).
    Janssen H, Wlodarska I, Mecucci C, Hagemeijer A, Vandenberghe P, Marynen P, Cools J.
    Haematologica. 2006 Jul;91(7):949-51. Epub 2006 Jun 1.
    PMID 16757412
    ETV6/GOT1 fusion in a case of t(10;12)(q24;p13)-positive myelodysplastic syndrome.
    Struski S, Mauvieux L, Gervais C, Helias C, Liu KL, Lessard M.
    Haematologica. 2008 Mar;93(3):467-8.
    PMID 18310541
    TEL gene is involved in myelodysplastic syndromes with either the typical t(5;12)(q33;p13) translocation or its variant t(10;12)(q24;p13).
    Wlodarska I, Mecucci C, Marynen P, Guo C, Franckx D, La Starza R, Aventin A, Bosly A, Martelli MF, Cassiman JJ, Van den Berghe H.
    Blood. 1995 May 15;85(10):2848-52.
    PMID 7742547


    This paper should be referenced as such :
    Wlodarska, I
    Atlas Genet Cytogenet Oncol Haematol. 2009;13(9):673-675.
    Free journal version : [ pdf ]   [ DOI ]
    On line version :

    Other genes implicated (Data extracted from papers in the Atlas) [ 1 ]

    Genes ETV6

    Translocations implicated (Data extracted from papers in the Atlas)

     t(10;12)(q24;p13) ETV6/GOT1

    External links

    ETV6 (12p13.2) GOT1 (10q24.2)

    ETV6 (12p13.2) GOT1 (10q24.2)

    Mitelman databaset(10;12)(q24;p13)
    arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9975/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
    arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9989/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
    Mitelman databaseETV6/GOT1 [MCList]  ETV6 (12p13.2) GOT1 (10q24.2)
    TICdbETV6/GOT1  ETV6 (12p13.2) GOT1 (10q24.2)
    REVIEW articlesautomatic search in PubMed
    Last year articlesautomatic search in PubMed
    All articlesautomatic search in PubMed

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    indexed on : Mon Sep 7 15:08:04 CEST 2020

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