t(8;12)(q13;p13) ETV6/NCOA2

2013-11-01   Jean-Loup Huret 

1.Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

Clinics and Pathology


T-cell acute lymphoblastic leukemia (T-ALL), B-cell acute lymphoblastic leukemia (B-ALL), biphenotypic acute leukemia (BAL), and acute myeloid leukemia (AML).

Phenotype stem cell origin

This entity most often appears as a childhood leukemia expressing both T-lymphoid and myeloid antigens. Eleven cases are available to date: one case of common B-ALL, 6 cases of T-ALL, 3 cases of BAL, and one M4-AML (Pui et al., 1987; Schneider et al., 2000; Yamamoto et al., 2002; Strehl et al., 2008; Zhou et al., 2012).


There were 5 male and 6 female patients, aged 2, 2, 2, 7, 8, 11, 14, 23, 75 years, and two additional cases came from a series of "childhood leukemia".
Atlas Image
Overall survival in patients with t(8;12)(q13;p13) ETV6/NCOA9 (n=9).


Although the sample is far too small for definitive conclusions, the prognosis does not seem bad (see Figure).

Genes Involved and Proteins

Heterozygous NOTCH1 mutations were found in five of six samples where they were studied (Strehl et al., 2008; Zhou et al., 2012).
Gene name
NCOA2 (nuclear receptor coactivator 2)
Protein description
1464 amino acids. NCOA2 is composed of a basic helix-loop-helix (HLH), a PAS (Per/Arnt/Sim) region, four LXXLL motifs (L=leucine, X=any amino acid) that are critical for interaction with nuclear receptors, a LLXXLXXXL motif is involved in transcriptional coactivation and CREBBP/CBP binding, and a polyglutamine tract. Transcriptional coactivator for steroid receptors and nuclear receptors. Involved in skeletal muscle differentiation (Chen et al., 2000). Acts as a tumor suppressor in liver cancer (ODonnell et al., 2012).
Gene name
ETV6 (ets variant 6)
Protein description
452 amino acids. ETV6 is composed of a HLH domain responsible for hetero- and homodimerization in N-term, and an ETS domain responsible for sequence specific DNA-binding in C-term (binds to the DNA sequence 5-CCGGAAGT-3). Transcriptional regulator; tumor suppressor. Involved in bone marrow hematopoiesis.

Result of the Chromosomal Anomaly


There was fusion of ETV6 exon 4 with NCOA2 exon 15 in five of six cases, and fusion of ETV6 exon 5 with NCOA2 exon 14 in one case (Strehl et al., 2008).Fuses the pointed or sterile alpha motif (SAM) oligomerization domain of ETV6 to the C-term poly Gln of NCOA2 (with or without the LLXXLXXXL motif of NCOA2).

Highly cited references

Pubmed IDYearTitleCitations
182815292008ETV6-NCOA2: a novel fusion gene in acute leukemia associated with coexpression of T-lymphoid and myeloid markers and frequent NOTCH1 mutations.19
316483212019Transcriptome analysis offers a comprehensive illustration of the genetic background of pediatric acute myeloid leukemia.17
223735492012Detection of ETV6 gene rearrangements in adult acute lymphoblastic leukemia.9
346240962022ETV6-NCOA2 fusion induces T/myeloid mixed-phenotype leukemia through transformation of nonthymic hematopoietic progenitor cells.1
282728052018Early thymic precursor-like lymphomatous presentation of the ETV6-NCOA2 translocation.0


Pubmed IDLast YearTitleAuthors
108177562000The steroid receptor coactivator, GRIP-1, is necessary for MEF-2C-dependent gene expression and skeletal muscle differentiation.Chen SL et al
225562672012A Sleeping Beauty mutagenesis screen reveals a tumor suppressor role for Ncoa2/Src-2 in liver cancer.O'Donnell KA et al
34740421987Hypodiploidy is associated with a poor prognosis in childhood acute lymphoblastic leukemia.Pui CH et al
110019092000New recurring cytogenetic abnormalities and association of blast cell karyotypes with prognosis in childhood T-cell acute lymphoblastic leukemia: a pediatric oncology group report of 343 cases.Schneider NR et al
182815292008ETV6-NCOA2: a novel fusion gene in acute leukemia associated with coexpression of T-lymphoid and myeloid markers and frequent NOTCH1 mutations.Strehl S et al
123774162002Translocation (8;12)(q13;p13) during disease progression in acute myelomonocytic leukemia with t(11;19)(q23;p13.1).Yamamoto K et al
223735492012Detection of ETV6 gene rearrangements in adult acute lymphoblastic leukemia.Zhou MH et al


Fusion gene

ETV6/NCOA2 ETV6 (12p13.2) NCOA2 (8q13.3) M t(8;12)(q13;p13)
Atlas Image
t(8;12)(q13;p13) - Courtesy Eric Crawford, Genetics Associates, Inc., Nashville, TN 37203, USA


Jean-Loup Huret

t(8;12)(q13;p13) ETV6/NCOA2

Atlas Genet Cytogenet Oncol Haematol. 2013-11-01

Online version: http://atlasgeneticsoncology.org/haematological/1503/t(8;12)(q13;p13)