t(1;12)(q21;p13) ETV6/ARNT

2013-09-01   Jean-Loup Huret 

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

Clinics and Pathology


Myeloid and lymphoid malignancies


Excluded from this review is a case of multiple myeloma (Lewis and MacKenzie, 1984).

Phenotype stem cell origin

Two cases of acute lympoblastic leukemia (ALL) have been described with a t(1;12)(q21;p13): an ALL not otherwise specified (NOS) in a female patient with no indication concerning the genes involved (Heerema et al., 2004), and a T-cell ALL (CD5+, CD7+, CD4-, CD8-) in a 2-year old boy, and with assessement of an ETV6/ARNT transcript (Otsubo et al., 2010). Three myeloid cases are available: a chronic myelogenous leukemia in blast crisis (BC-CML) in a female patient without molecular data (Palandri et al., 2009), a M2 acute myeloblastic leukemia (M2-AML) in a 5-year old boy with an ETV6/ARNT transcript (Berger et al., 1997; Salomon-Nguyen et al., 2000), and a case of refractory anemia with excess blasts in transformation (RAEB-t) with total absence of erythroid precursors in bone marrow in a 64-year old male patient, where ETV6 may not be involved (Sánchez et al., 2000).


In this small series, 2 of 3 cases, however, are found in pediatric patients.


Very scarce data: the BC-CML patient died 47 months after diagnosis.

Genes Involved and Proteins

An ETV6/ARNT hybrid transcript has therefore been described in two cases: a case of T-ALL, and a case of M2-AML. The breakpoint appears to be identical in the two cases: ETV6 exon 4 fused to the ARNT exon 2 (Otsubo et al., 2010), breakpoint after the 154 first amino acids in ETV6 and after the 8 first amino acids in ARNT (Salomon-Nguyen et al., 2000).
Gene name
ARNT (aryl hydrocarbon receptor nuclear translocator)
Protein description
789 amino acids. ARNT is composed of a bHLH, basic helix-loop-helix domain, 2PAS, Per/ARNT/Sim homology domains, and a glutamine-rich transactivation domain. Transcription factor. Forms homodimers or hetrodimers with AHR (7p21); mediates the cellular response to xenobiotic compounds such as environmental pollutants. Interacts with estrogen receptors (ER). ARNT is recruited to estrogen-responsive promoters, leading to increased ER transcription (reviews in Hankinson, 2004; Swedenborg and Pongratz, 2010).
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


ETV6 exon 4 was fused in frame to the ARNT exon 2 (Otsubo et al., 2010).
Atlas Image


Two fusion proteins are found as a result of this translocation. The ETV6/ARNT protein contains the 154 first amino acids, including the aminoterminal oligomerization domain of ETV6 and most of the ARNT protein, and is highly expressed in the leukemic cells of the patient (Salomon-Nguyen et al., 2000). The ARNT/ETV6 protein contains the first 8 amino acids of ARNT fused to the 298 carboxyl-terminal amino acids of ETV6 including its ETS DNA-binding domain. This protein is hardly expressed and is likely to be not involved in the malignant process (Salomon-Nguyen et al., 2000).

Highly cited references

Pubmed IDYearTitleCitations
208049162010ETV6-ARNT fusion in a patient with childhood T lymphoblastic leukemia.6
351927452022Genetic analysis and clinical significance of a rare t(1;12)(q21;p13) in a patient with high-risk myelodysplastic syndrome.1


Pubmed IDLast YearTitleAuthors
93055911997Chromosome abnormalities of the short arm of chromosome 12 in hematopoietic malignancies: a report including three novel translocations involving the TEL/ETV6 gene.Berger R et al
149992942004Deletion of 7p or monosomy 7 in pediatric acute lymphoblastic leukemia is an adverse prognostic factor: a report from the Children's Cancer Group.Heerema NA et al
63354831984Non-random chromosomal aberrations associated with multiple myeloma.Lewis JP et al
208049162010ETV6-ARNT fusion in a patient with childhood T lymphoblastic leukemia.Otsubo K et al
191446562009The long-term durability of cytogenetic responses in patients with accelerated phase chronic myeloid leukemia treated with imatinib 600 mg: the GIMEMA CML Working Party experience after a 7-year follow-up.Palandri F et al
108290782000The t(1;12)(q21;p13) translocation of human acute myeloblastic leukemia results in a TEL-ARNT fusion.Salomon-Nguyen F et al
107563752000A case of atypical myelodysplastic syndrome with a novel reciprocal translocation t(1;12)(q21;p13).Sánchez J et al
197785762010AhR and ARNT modulate ER signaling.Swedenborg E et al


Fusion gene

ETV6/ARNT ETV6 (12p13.2) ARNT (1q21.3) M t(1;12)(q21;p13)|ETV6/ARNT ETV6 (12p13.2) ARNT (1q21.3) TIC


Jean-Loup Huret

t(1;12)(q21;p13) ETV6/ARNT

Atlas Genet Cytogenet Oncol Haematol. 2013-09-01

Online version: http://atlasgeneticsoncology.org/haematological/1171/t(1;12)(q21;p13)