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t(3;12)(q26;p13) ETV6::MECOM

t(3;12)(q26;p13) ETV6::EVI1

Written2014-04Etienne De Braekeleer, Nathalie Douet-Guilbert, Marc De Braekeleer
Cytogenetics Laboratory, Faculty of Medicine, University of Brest, France
This article is an update of :
1997-09François Desangles
Laboratoire de Biologie, Hopital du Val de Grace, 75230 Paris, France

(Note : for Links provided by Atlas : click)


ICD-Morpho 9861/3 AML with mutated NPM1; AML with mutated CEBPA; Acute myeloid leukaemia, NOS
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 1008
Note Only a few cases were shown to involve a ETV6/MECOM fusion by FISH or RT-PCR. In other cases, only MECOM or ETV6 was shown to be rearranged by FISH. Over-expression of MECOM/EVI1 was found in other cases. Finally, no cytogenetic or molecular analysis was performed in a few cases.
  t(3;12)(q26;p13) ETV6/MECOM left: G-banding - Courtesy Jean-Luc Lai and Alain Vanderhaegen; right: R-banded karyotype (top) and FISH using the double break apart probes MECOM/3q26 (Metasystems)(bottom left) and ETV6 /12p13 (Abbott)(bottom right). Courtesy Karolien Beel, Peter Meeus and Lucienne Michaux, CME, UZ Leuven.

Clinics and Pathology

Disease Myeloid lineage: MDS in transformation, AML, BC-CML
Phenotype / cell stem origin Multilineage involvement; MDS--> M0, M2, M4, M7.
Epidemiology 46 cases described so far; sex ratio: 29M/16F (1 unknown); age: 2.5-87 yrs (med: 49 yrs), unknown age for 10 cases.
Cytology Dysplasia of megakaryocytes, multilineage involvement.
Survival curve (21 patients, Mean: 12 mths, Median: 10 mths).
Prognosis See survival curve above.


Cytogenetics Molecular Heterogeneity of the EVI1 breakpoints, as evidenced by the Cytocell Aquarius EVI1 Breakapart probe. The EVI1 Breakapart probe contains three probes: a probe labeled in Aqua of 562 kb in size centromeric to the EVI1 gene, a probe labeled in Spectrum Green of 181 kb covering EVI1 and its flanking regions and a probe labeled in Spectrum Orange of 124 kb telomeric of the EVI1 gene (telomeric of MYNN and covering LRRC34).
Additional anomalies Sole anomaly in 22 cases. Additional anomalies: t(9;22)(q34;q11) in 5 cases, -7/del(7q) in 11 cases, del(5q) in 2 cases, others in 6 cases.

Genes involved and Proteins

Gene NameMECOM (Ecotropic Viral Integration Site 1 (EVI1) and Myelodysplastic Syndrome 1 (MDS1-EVI1)
Location 3q26.2
Note Alias EVI1
Dna / Rna MECOM is a "complex entity" made of two genes, EVI1 and MDS1. EVI1 has 16 exons, of which 14 are coding, the start ATG codons being in exon 3. MDS1 has 4 exons, exon 4 being located in the vicinity of exon 1 of EVI1. Splicing of the second exon of MDS1 to the second exon of EVI1 leads to a MDS1-EVI1 mRNA.
Protein EVI1 contains two domains of seven and three zinc finger motifs separated by a repression domain and an acidic domain at its C-terminus.
Gene NameETV6 (ets variant 6)
Location 12p13.2
Note The ETV6 gene encodes a transcription factor frequently rearranged in myeloid and lymphoid leukemias.
Dna / Rna The ETV6 gene spans a region of less than 250 kb at band 12p13.1 and consists of 8 exons. There are two start codons, one (exon 1a starting at codon 1) located at the beginning of the gene and another alternative (exon 1b starting at codon 43) upstream of exon 3.
Protein The ETV6 protein (452 amino acids) contains two major domains, the HLH (helix-loop-helix) and ETS domains. The HLH domain, also referred to as the pointed or sterile alpha motif domain, is encoded by exons 3 and 4 and functions as a homo-oligodimerization domain. The ETS domain, encoded by exons 6 through 8, is responsible for sequence specific DNA-binding and protein-protein interaction.

Result of the chromosomal anomaly

Hybrid gene
Description Two mechanisms for generating the fusion gene, depending upon the involvement of the MDS1 gene.
Transcript 1) In-frame transcript consisting of the first two exons of ETV6 fused to MDS1 sequences, which in turn is fused to the second exon of the EVI1 gene.
2) Out-of-frame fusion by direct fusion between exon 2 of ETV6 and exon 2 of EVI1, but keeping the open reading frame of EVI1 intact.
Fusion Protein
  Schematic diagram of the ETV6, EVI1, MDS1, MDS1-EVI1, ETV6-EVI1 and ETV6-MDS1-EVI1 proteins.
Description ETV6 contributes no known functional domain to the predicted chimeric protein but functional domains of EVI1 are retained.
Oncogenesis The oncogenic potential of the translocation could be the result of the ETV6 promoter driving the transcription of EVI1. Because the ETV6 promoter is active in hematopoietic cells, this would result in inappropriate expression of the transcription factor EVI1.


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This paper should be referenced as such :
Braekeleer E De, N Douet-Guilbert, Braekeleer M De
t(3;12)(q26;p13) ETV6/MECOM - t(3;12)(q26;p13) ETV6/EVI1
Atlas Genet Cytogenet Oncol Haematol. 2014;18(12):950-953.
Free journal version : [ pdf ]   [ DOI ]
On line version :
History of this paper:
Desangles, F. t(3;12)(q26;p13). Atlas Genet Cytogenet Oncol Haematol. 1997;1(1):22-22.

Other genes implicated (Data extracted from papers in the Atlas) [ 2 ]


Translocations implicated (Data extracted from papers in the Atlas)

 t(3;12)(q26;p13) ETV6/MECOM

External links

ETV6 (12p13.2) MECOM (3q26.2)

ETV6 (12p13.2) MECOM (3q26.2)

Mitelman databaset(3;12)(q26;p13)
arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9861/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
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::MECOM [MCList]  ETV6 (12p13.2) MECOM (3q26.2)
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed
All articlesautomatic search in PubMed

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