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

Written2013-11Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

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ICD-Morpho 9811/3 B lymphoblastic leukaemia/lymphoma, NOS
ICD-Morpho 9837/3 T lymphoblastic leukaemia/lymphoma
ICD-Morpho 9861/3 AML with mutated NPM1; AML with mutated CEBPA; Acute myeloid leukaemia, NOS
Atlas_Id 1503
  t(8;12)(q13;p13) - Courtesy Eric Crawford, Genetics Associates, Inc., Nashville, TN 37203, USA

Clinics and Pathology

Disease T-cell acute lymphoblastic leukemia (T-ALL), B-cell acute lymphoblastic leukemia (B-ALL), biphenotypic acute leukemia (BAL), and acute myeloid leukemia (AML).
Phenotype / cell stem 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).
Epidemiology 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".
Overall survival in patients with t(8;12)(q13;p13) ETV6/NCOA9 (n=9).
Prognosis Although the sample is far too small for definitive conclusions, the prognosis does not seem bad (see Figure).


Cytogenetics Morphological Breakpoints were difficult to assign accurately by conventional cytogenetics, with cases described with a t(8;12)(q10;p10), a t(8;12)(q11;p11), a t(8;12)(q12;p12), a t(8;12)(q12;p13), or a t(8;12)(q13;p13), but all exhibiting an ETV6/NCOA2 fusion transcript (Strehl et al., 2008). The t(8;12) was the sole anomaly in five cases (four ALLs and one M1-AML/BAL), and was accompanied with a del(5q) in two ALL cases, a del(6q), a +9, and a del(11q) in an ALL each, a t(11;19)(q23;p13) in the M4-AML, and a +22 in a M1-AML/BAL.

Genes involved and Proteins

Note Heterozygous NOTCH1 mutations were found in five of six samples where they were studied (Strehl et al., 2008; Zhou et al., 2012).
Gene NameNCOA2 (nuclear receptor coactivator 2)
Location 8q13.3
Protein 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 (O'Donnell et al., 2012).
Gene NameETV6 (ets variant 6)
Location 12p13.2
Protein 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

Hybrid gene
Description 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).
Fusion Protein
Description 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).

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.


The steroid receptor coactivator, GRIP-1, is necessary for MEF-2C-dependent gene expression and skeletal muscle differentiation.
Chen SL, Dowhan DH, Hosking BM, Muscat GE.
Genes Dev. 2000 May 15;14(10):1209-28.
PMID 10817756
A Sleeping Beauty mutagenesis screen reveals a tumor suppressor role for Ncoa2/Src-2 in liver cancer.
O'Donnell KA, Keng VW, York B, Reineke EL, Seo D, Fan D, Silverstein KA, Schrum CT, Xie WR, Mularoni L, Wheelan SJ, Torbenson MS, O'Malley BW, Largaespada DA, Boeke JD.
Proc Natl Acad Sci U S A. 2012 May 22;109(21):E1377-86. doi: 10.1073/pnas.1115433109. Epub 2012 May 3.
PMID 22556267
Hypodiploidy is associated with a poor prognosis in childhood acute lymphoblastic leukemia.
Pui CH, Williams DL, Raimondi SC, Rivera GK, Look AT, Dodge RK, George SL, Behm FG, Crist WM, Murphy SB.
Blood. 1987 Jul;70(1):247-53.
PMID 3474042
New 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, Carroll AJ, Shuster JJ, Pullen DJ, Link MP, Borowitz MJ, Camitta BM, Katz JA, Amylon MD.
Blood. 2000 Oct 1;96(7):2543-9.
PMID 11001909
ETV6-NCOA2: a novel fusion gene in acute leukemia associated with coexpression of T-lymphoid and myeloid markers and frequent NOTCH1 mutations.
Strehl S, Nebral K, Konig M, Harbott J, Strobl H, Ratei R, Struski S, Bielorai B, Lessard M, Zimmermann M, Haas OA, Izraeli S.
Clin Cancer Res. 2008 Feb 15;14(4):977-83. doi: 10.1158/1078-0432.CCR-07-4022.
PMID 18281529
Translocation (8;12)(q13;p13) during disease progression in acute myelomonocytic leukemia with t(11;19)(q23;p13.1).
Yamamoto K, Nagata K, Tsurukubo Y, Inagaki K, Ono R, Taki T, Hayashi Y, Hamaguchi H.
Cancer Genet Cytogenet. 2002 Aug;137(1):64-7.
PMID 12377416
Detection of ETV6 gene rearrangements in adult acute lymphoblastic leukemia.
Zhou MH, Gao L, Jing Y, Xu YY, Ding Y, Wang N, Wang W, Li MY, Han XP, Sun JZ, Wang LL, Yu L.
Ann Hematol. 2012 Aug;91(8):1235-43. doi: 10.1007/s00277-012-1431-4. Epub 2012 Feb 29.
PMID 22373549


This paper should be referenced as such :
Huret, JL
t(8;12)(q13;p13) ETV6/NCOA2
Atlas Genet Cytogenet Oncol Haematol. 2014;18(6):436-437.
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(8;12)(q13;p13) ETV6/NCOA2

External links

ETV6 (12p13.2) NCOA2 (8q13.3)

Mitelman databaset(8;12)(q13;p13)
arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9811/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9837/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9861/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
Mitelman databaseETV6::NCOA2 [MCList]  ETV6 (12p13.2) NCOA2 (8q13.3)
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed
All articlesautomatic search in PubMed

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indexed on : Fri Oct 8 16:36:56 CEST 2021

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