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

Written2013-09Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

(Note : for Links provided by Atlas : click)

Identity

ICD-Topo C420,C421,C424 BLOOD, BONE MARROW, & HEMATOPOIETIC SYS
ICD-Morpho 9837/3 T lymphoblastic leukaemia/lymphoma
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 1171

Clinics and Pathology

Disease Myeloid and lymphoid malignancies
Note Excluded from this review is a case of multiple myeloma (Lewis and MacKenzie, 1984).
Phenotype / cell stem 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).
Epidemiology In this small series, 2 of 3 cases, however, are found in pediatric patients.
Prognosis Very scarce data: the BC-CML patient died 47 months after diagnosis.

Cytogenetics

Cytogenetics Morphological A del(7q) was found in an ALL case, a t(9;22)(q34;q11) in the BC-CML case, indeed, and the t(1;12) was the sole anomaly in the RAEB-t case.

Genes involved and Proteins

Note 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 NameARNT (aryl hydrocarbon receptor nuclear translocator)
Location 1q21.3
Protein 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 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 ETV6 exon 4 was fused in frame to the ARNT exon 2 (Otsubo et al., 2010).
  
Fusion Protein
 
Description 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).
  

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.

Bibliography

Chromosome abnormalities of the short arm of chromosome 12 in hematopoietic malignancies: a report including three novel translocations involving the TEL/ETV6 gene.
Berger R, Le Coniat M, Lacronique V, Daniel MT, Lessard M, Berthou C, Marynen P, Bernard O.
Leukemia. 1997 Sep;11(9):1400-3.
PMID 9305591
 
ARNT (aryl hydrocarbon receptor nuclear translocator).
Hankinson O.
Atlas Genet Cytogenet Oncol Haematol. 2004; 8(4):313-315. http://AtlasGeneticsOncology.org/Genes/ARNTID223ch1q21.html
 
Deletion 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, Nachman JB, Sather HN, La MK, Hutchinson R, Lange BJ, Bostrom B, Steinherz PG, Gaynon PS, Uckun FM; Children's Cancer Group.
Leukemia. 2004 May;18(5):939-47.
PMID 14999294
 
Non-random chromosomal aberrations associated with multiple myeloma.
Lewis JP, MacKenzie MR.
Hematol Oncol. 1984 Oct-Dec;2(4):307-17.
PMID 6335483
 
ETV6-ARNT fusion in a patient with childhood T lymphoblastic leukemia.
Otsubo K, Kanegane H, Eguchi M, Eguchi-Ishimae M, Tamura K, Nomura K, Abe A, Ishii E, Miyawaki T.
Cancer Genet Cytogenet. 2010 Oct 1;202(1):22-6. doi: 10.1016/j.cancergencyto.2010.07.121.
PMID 20804916
 
The 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, Castagnetti F, Alimena G, Testoni N, Breccia M, Luatti S, Rege-Cambrin G, Stagno F, Specchia G, Martino B, Levato L, Merante S, Liberati AM, Pane F, Saglio G, Alberti D, Martinelli G, Baccarani M, Rosti G.
Haematologica. 2009 Feb;94(2):205-12. doi: 10.3324/haematol.13529. Epub 2009 Jan 14.
PMID 19144656
 
The t(1;12)(q21;p13) translocation of human acute myeloblastic leukemia results in a TEL-ARNT fusion.
Salomon-Nguyen F, Della-Valle V, Mauchauffe M, Busson-Le Coniat M, Ghysdael J, Berger R, Bernard OA.
Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6757-62.
PMID 10829078
 
A case of atypical myelodysplastic syndrome with a novel reciprocal translocation t(1;12)(q21;p13).
Sanchez J, Serrano J, Roman J, Garcia JM, Nomdedeu J, Torres A.
Haematologica. 2000 Apr;85(4):434-5.
PMID 10756375
 
AhR and ARNT modulate ER signaling.
Swedenborg E, Pongratz I.
Toxicology. 2010 Feb 9;268(3):132-8. doi: 10.1016/j.tox.2009.09.007. Epub 2009 Sep 22. (REVIEW)
PMID 19778576
 

Citation

This paper should be referenced as such :
Huret, JL
t(1;12)(q21;p13) ETV6/ARNT
Atlas Genet Cytogenet Oncol Haematol. 2014;18(3):197-199.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Anomalies/t0112q21p13ID1171.html


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

Genes ARNT ETV6

Translocations implicated (Data extracted from papers in the Atlas)

 t(1;12)(q21;p13) ETV6/ARNT

External links

ETV6 (12p13.2) ARNT (1q21.3)

ETV6 (12p13.2) ARNT (1q21.3)

Mitelman databaset(1;12)(q21;p13) [Case List]    t(1;12)(q21;p13) [Association List] Mitelman database (CGAP - NCBI)
arrayMapTopo ( C42) Morph ( 9837/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMapTopo ( C42) Morph ( 9975/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMapTopo ( C42) Morph ( 9989/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
 
Mitelman databaseETV6/ARNT [MCList]  ETV6 (12p13.2) ARNT (1q21.3)
TICdbETV6/ARNT  ETV6 (12p13.2) ARNT (1q21.3)
 
Disease databaset(1;12)(q21;p13) ETV6/ARNT
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed
All articlesautomatic search in PubMed


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