8q24 amplified segments involve novel fusion genes between NSMCE2 and long noncoding RNAs in acute myelogenous leukemia
© Chinen et al.; licensee BioMed Central Ltd. 2014
Received: 2 September 2014
Accepted: 11 September 2014
Published: 23 September 2014
The pathogenetic roles of 8q24 amplified segments in leukemic cells with double minute chromosomes remain to be verified. Through comprehensive molecular analyses of 8q24 amplicons in leukemic cells from an acute myelogenous leukemia (AML) patient and AML-derived cell line HL60 cells, we identified two novel fusion genes between NSMCE2 and long noncoding RNAs (lncRNAs), namely, PVT1-NSMCE2 and BF104016-NSMCE2. Our study suggests that 8q24 amplicons are associated with the emergence of aberrant chimeric genes between NSMCE2 and oncogenic lncRNAs, and also implicate that the chimeric genes involving lncRNAs potentially possess as-yet-unknown oncogenic functional roles.
KeywordsAcute myeloid leukemia (AML) Long noncoding RNAs (lincRNAs) PVT1 NSMCE2 CCDC26
To the Editor
The present findings are consistent with previous studies demonstrating that segmental genome amplification of 8q24 contains recurrent PVT1 fusion genes, which might be generated by chromothripsis ,. Both lncRNAs, PVT1 and CCDC26, harbor retroviral integration sites and are transcribed into multiple splice forms -. PVT1 overexpression is induced by MYC or p53, contributing to suppression of apoptosis -, whereas PVT1 produces six annotated microRNAs that have been implicated in oncogenesis ,,. The chimeric transcripts involving PVT1 may also regulate the expression of as-yet unspecified target genes through ‘enhancer-like functions’ . CCDC26 amplification has been also identified as a recurrent abnormality that is associated with the response to retinoic acid-induced differentiation in AML ,,-. This study is the first to identify NSMCE2-associated fusion genes in AML -. Knockdown of NSMCE2 induces chromosomal instability and increases the frequency of chromosomal breakage and loss . We speculate that NSMCE2 gene rearrangement may potentially influence its function. Collectively, our study identified novel PVT1-NSMCE2 and CCDC26-NSMCE2 fusion genes that may play functional roles in leukemia.
YC, JK and MT reviewed the literature and wrote the paper. YC, MYS, SM, and SH treated the patient. NS, HN, TT, SM, ST, TT, YS, TK, YM and MT collected the data. YC and NS performed the molecular analyses. YC, JK and MT contributed to the design of this study, final data analysis and edited the manuscript. All authors read and approved the final manuscript.
Double minute chromosomes
Homogeneously staining regions
Fluorescence in situ hybridization
Long noncoding RNAs
Acute myeloid leukemia
Non-SMC element 2
Reverse transcription-polymerase chain reaction
Long-distance inverse PCR
The authors thank Akari Kazami and Yoko Yamane for their expert technical assistance. This study was performed as a research program of the Project for Development of Innovative Research on Cancer Therapeutics (P-Direct), Ministry of Education, Culture, Sports, Science and Technology of Japan, and supported by a Grant-in-Aid for Cancer Research from the Ministry of Health, Labor and Welfare of Japan, by a Grant-in-aid for Scientific Research (B) and (C) from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and by the National Cancer Center Research and Development Fund.
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