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t(3;21)(q26;q11) NRIP1/MECOM

Written2016-07Jean Loup Huret
Medical Genetics, Dept Medical Information, University Hospital, F-86021 Poitiers, France. Jean-loup.huret@chu-poitiers.fr

Abstract Review on t(3;21)(q26;q11), with data on clinics, and the genes involved.

Keywords chromosome 3; chromosome 21; t(3;21)(q26;q11); MECOM; NRIP1

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Identity

ICD-Topo C420,C421,C424
ICD-Morpho 9865/3 AML with t(6;9)(p23;q34); DEK-NUP214v AML with inv(3)(q21q26.2) or t(3;3)(q21;q26.2);RPN1-EVI1
ICD-Morpho 9861/3 AML with mutated NPM1; AML with mutated CEBPA; Acute myeloid leukaemia, NOS
ICD-Morpho 9989/3 Myelodysplastic syndrome, unclassifiable
Atlas_Id 1464

Clinics and Pathology

Note Ten cases available, but with almost no data (Bobadilla et al., 2007; Haferlach et al., 2012).
Phenotype / cell stem origin Out of ten cases, there were four acute myeloid leukemia (AML) cases, and six myelodysplastic syndromes (MDS)
Epidemiology t(3;21)(q26;q11) represented about 1% of a cohort of 606 AML and 377 MDS patients with normal karyotypes (n = 594) or chromosome 7 alterations (-7/7q-; n = 389). Median age was 49 years (range 25-76) (Haferlach et al., 2012).
Clinics Median WBC count was 60.0 × 109/L (range 2.4-15.0)
Cytogenetics Cryptic rearrangement.
Prognosis Survival outcomes in 22 patients with cryptic MECOM rearrangements (t(3;21)(q26;q11), inv(3)(p24q26), and der(7)t(3;7)(q26;q21) altogether) and were compared with inv(3)(q21q26)/t(3;3)(q21;q26) cases. Median overall survival was 9.4 months in the subgroup with cryptic MECOM rearrangements which was not significantly different from the 21.8 months in patients with an inv(3)(q21q26)/t(3;3)(q21;q26) (Haferlach et al., 2012).

Genes involved and Proteins

Gene NameMECOM (Ecotropic Viral Integration Site 1 (EVI1) and Myelodysplastic Syndrome 1 (MDS1-EVI1)
Location 3q26.2
Note MECOM is a nuclear transcription factor that plays an essential role in the proliferation and maintenance of hematopoietic stem cells and can inhibit myeloid differentiation. Two alternative forms exists, one generated from EVI1, the other MECOM (MDS1 and EVI1 complex locus) through intergenic splicing with MDS1 (myelodysplasia syndrome 1), a gene located 140 kb upstream of EVI1.
Protein The protein encoded by this gene is a transcriptional regulator involved in cell differentiation and proliferation, and apoptosis. The encoded protein can interact with transcriptional coactivators (P/CAF, CBP) and corepressors (CTBP1, HDAC) as well as other transcription factors (GATA1, Smad3) (de Braekeleer et al., 2012)
Gene NameNRIP1 (nuclear receptor interacting protein 1)
Location 21q11.2
Protein is a co-repressor of a large number of nuclear receptors. NRIP1 interacts preferentially with ligand-bound nuclear receptors and inhibits transactivation by recruitment of histone deacetylases and CtBP. NRIP1 interacts with ESR2 (Estrogen Receptor 2 (ER beta)) in ovarian cancer cells and ESR2 and E2F (in particular E2F1) transcription factors in breast cancer cells, represses their transcriptional activities and inhibits cell proliferation. NRIP1 ncreases APC expression exerting a negative control on the Wnt/ β-catenin signaling in human colon cancer cells. Repression of CTNNB1 (β-catenin) by NRIP1 has also been described in hepatocellular carcinoma (Spinella, 2010; Lapierre et al., 2015).

Result of the chromosomal anomaly

Hybrid gene
Description Breakpoints were located in introns 2 or 4 in EVI1, and in introns 1, 2, or 3 in NRIP1 (Haferlach et al., 2012).
  
Fusion Protein
Oncogenesis Increased MECOM expression was noted.
  

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

An interphase fluorescence in situ hybridisation assay for the detection of 3q26.2/EVI1 rearrangements in myeloid malignancies.
Bobadilla D, Enriquez EL, Alvarez G, Gaytan P, Smith D, Slovak ML.
Br J Haematol. 2007 Mar;136(6):806-13.
PMID 17341266
 
Three novel cytogenetically cryptic EVI1 rearrangements associated with increased EVI1 expression and poor prognosis identified in 27 acute myeloid leukemia cases.
Haferlach C, Bacher U, Grossmann V, Schindela S, Zenger M, Kohlmann A, Kern W, Haferlach T, Schnittger S.
Genes Chromosomes Cancer. 2012 Dec;51(12):1079-85. doi: 10.1002/gcc.21992. Epub 2012 Aug 8.
PMID 22887804
 
The emerging role of the transcriptional coregulator RIP140 in solid tumors.
Lapierre M, Docquier A, Castet-Nicolas A, Gitenay D, Jalaguier S, Teyssier C, Cavaills V.
Biochim Biophys Acta. 2015 Aug;1856(1):144-50. doi: 10.1016/j.bbcan.2015.06.006. Epub 2015 Jun 25. Review
PMID 26116758
 
NRIP1 (nuclear receptor interacting protein 1)
Spinella MJ
Atlas Genet Cytogenet Oncol Haematol. 2010;14(10):923-925.
 
inv(3)(q21q26)x2
de Braekeleer E, Douet-Guilbert, N, Le Bris MJ, Basink A, Morel F, de Braekeleer M.
Atlas Genet Cytogenet Oncol Haematol. 2013;17(7):491-493.
 

Citation

This paper should be referenced as such :
Huret JL
t(3;21)(q26;q11) NRIP1/MECOM;
Atlas Genet Cytogenet Oncol Haematol. in press
On line version : http://AtlasGeneticsOncology.org/Anomalies/t0321q26q11ID1464.html


Translocations implicated (Data extracted from papers in the Atlas)

 t(3;21)(q26;q11) NRIP1/MECOM

External links

Mitelman databaset(3;21)(q26;q11) [Case List]    t(3;21)(q26;q11) [Association List] Mitelman database (CGAP - NCBI)
arrayMapMorph ( 9865/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMapMorph ( 9861/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMapMorph ( 9989/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
 
 
Disease databaset(3;21)(q26;q11) NRIP1/MECOM
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed
All articlesautomatic search in PubMed


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