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

2016-07-01   Jean Loup Huret 

1.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.

Clinics and Pathology

Noted

Ten cases available, but with almost no data (Bobadilla et al., 2007; Haferlach et al., 2012).

Phenotype stem cell 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 name
MECOM (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 description
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 name
NRIP1 (nuclear receptor interacting protein 1)
Location
21q11.2
Protein description
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

Description

Breakpoints were located in introns 2 or 4 in EVI1, and in introns 1, 2, or 3 in NRIP1 (Haferlach et al., 2012).

Oncogenesis

Increased MECOM expression was noted.

Highly cited references

Pubmed IDYearTitleCitations
331473382020Whole transcriptome sequencing detects a large number of novel fusion transcripts in patients with AML and MDS.9

Bibliography

Pubmed IDLast YearTitleAuthors
173412662007An interphase fluorescence in situ hybridisation assay for the detection of 3q26.2/EVI1 rearrangements in myeloid malignancies.Bobadilla D et al
228878042012Three novel cytogenetically cryptic EVI1 rearrangements associated with increased EVI1 expression and poor prognosis identified in 27 acute myeloid leukemia cases.Haferlach C et al
261167582015The emerging role of the transcriptional coregulator RIP140 in solid tumors.Lapierre M et al

Summary

Fusion gene

NRIP1/MECOM

Citation

Jean Loup Huret

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

Atlas Genet Cytogenet Oncol Haematol. 2016-07-01

Online version: http://atlasgeneticsoncology.org/haematological/1464/t(3;21)(q26;q11)