Aberrant pre-mRNA splicing of a highly conserved cell cycle regulator, CDC25C, in myelodysplastic syndromes

Abstract

Alternative pre-mRNA splicing alters gene expression and protein function, and aberrant splicing patterns can be associated with neoplasia. The potential role of disordered RNA splicing in myelodysplastic syndrome (MDS) is unexplored. We analysed the splicing repertoire of CDC25C– a gene localised to chromosome 5q31 and encoding a cyclin/cyclin-dependent-kinase regulatory phosphatase critical for cell cycle checkpoint control – in MDS, acute myeloid leukemia, chronic lymphocytic leukemia and healthy tissues. Five novel splicing isoforms were detected, and the splicing patterns were generally distinct in neoplastic samples compared with healthy controls. One of the novel isoforms, which we have termed CDC25C-6, occurred in 58% of the samples in our cohort. The results of this study suggest the possibility of aberrant splicing contributing to the phenotype in MDS and other haematologic malignancies.

Keywords:

• Alternative splicing
• cdc25c
• cell cycle regulator
• MDS
• 5q-syndrome