t(3;12)(q26;p13) ETV6/MECOM
t(3;12)(q26;p13) ETV6/EVI1

2014-04-01   Etienne De Braekeleer , Etienne De Braekeleer , Etienne De Braekeleer 

1.Cytogenetics Laboratory, Faculty of Medicine, University of Brest, France

Clinics and Pathology


Myeloid lineage: MDS in transformation, AML, BC-CML

Phenotype stem cell origin

Multilineage involvement; MDS--> M0, M2, M4, M7.


46 cases described so far; sex ratio: 29M/16F (1 unknown); age: 2.5-87 yrs (med: 49 yrs), unknown age for 10 cases.


Dysplasia of megakaryocytes, multilineage involvement.
Atlas Image
Survival curve (21 patients, Mean: 12 mths, Median: 10 mths).


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 name
MECOM (Ecotropic Viral Integration Site 1 (EVI1) and Myelodysplastic Syndrome 1 (MDS1-EVI1)
Alias EVI1
Dna rna description
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 description
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 name
ETV6 (ets variant 6)
The ETV6 gene encodes a transcription factor frequently rearranged in myeloid and lymphoid leukemias.
Dna rna description
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 description
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


Two mechanisms for generating the fusion gene, depending upon the involvement of the MDS1 gene.


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.
Atlas Image
Schematic diagram of the ETV6, EVI1, MDS1, MDS1-EVI1, ETV6-EVI1 and ETV6-MDS1-EVI1 proteins.


ETV6 contributes no known functional domain to the predicted chimeric protein but functional domains of EVI1 are retained.


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.

Highly cited references

Pubmed IDYearTitleCitations
316483212019Transcriptome analysis offers a comprehensive illustration of the genetic background of pediatric acute myeloid leukemia.17


Pubmed IDLast YearTitleAuthors
173412662007An interphase fluorescence in situ hybridisation assay for the detection of 3q26.2/EVI1 rearrangements in myeloid malignancies.Bobadilla D et al
86436841996Intergenic splicing of MDS1 and EVI1 occurs in normal tissues as well as in myeloid leukemia and produces a new member of the PR domain family.Fears S et al
81681371994Fusion of PDGF receptor beta to a novel ets-like gene, tel, in chronic myelomonocytic leukemia with t(5;12) chromosomal translocation.Golub TR et al
221622882012ETV6 rearrangements are recurrent in myeloid malignancies and are frequently associated with other genetic events.Haferlach C et al
118353392002Expression of the TEL/EVI1 fusion transcript in a patient with chronic myelogenous leukemia with t(3;12)(q26;p13).Nakamura Y et al
94478151997The EVI1 gene in myeloid leukemia.Nucifora G et al
218728262011Frequent EVI1 translocations in myeloid blast crisis CML that evolves through tyrosine kinase inhibitors.Paquette RL et al
90448251997Fusion of ETV6 to MDS1/EVI1 as a result of t(3;12)(q26;p13) in myeloproliferative disorders.Peeters P et al
163421722006EVI1 is consistently expressed as principal transcript in common and rare recurrent 3q26 rearrangements.Poppe B et al
86958161996Fluorescence in situ hybridization analysis of t(3; 12)(q26; p13): a recurring chromosomal abnormality involving the TEL gene (ETV6) in myelodysplastic syndromes.Raynaud SD et al
85471011995Abnormalities of 3q21 and 3q26 in myeloid malignancy: a United Kingdom Cancer Cytogenetic Group study.Secker-Walker LM et al
90675731997The leukemia-associated gene MDS1/EVI1 is a new type of GATA-binding transactivator.Soderholm J et al
125552182003Acute myelogenous leukemia with the t(3;12)(q26;p13) translocation: case report and review of the literature.Voutsadakis IA et al
175071832007The oncogene and developmental regulator EVI1: expression, biochemical properties, and biological functions.Wieser R et al
110217612000Breakpoint analysis by fluorescence in situ hybridization in myelodysplastic syndromes with t(3;12)(q26;p13) and expression of EVI1.van de Loosdrecht AA et al


Fusion gene

ETV6/MECOM ETV6 (12p13.2) MECOM (3q26.2) M t(3;12)(q26;p13)|ETV6/MECOM ETV6 (12p13.2) MECOM (3q26.2) TIC


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.
Atlas Image
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.


Etienne De Braekeleer ; Etienne De Braekeleer ; Etienne De Braekeleer

t(3;12)(q26;p13) ETV6/MECOM
t(3;12)(q26;p13) ETV6/EVI1

Atlas Genet Cytogenet Oncol Haematol. 2014-04-01

Online version: http://atlasgeneticsoncology.org/haematological/1008/t(3;12)(q26;p13)

Historical Card

1997-09-01 t(3;12)(q26;p13) ETV6/MECOM
t(3;12)(q26;p13) ETV6/EVI1
 by  François Desangles