Aberrant pre-mRNA splicing of a highly conserved cell cycle regulator, CDC25C, in myelodysplastic syndromes.
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.
Caudill
Jonathan S
JS
Division of Paediatric Haematology/Oncology, Mayo Clinic, Rochester, Minnesota, USA.
Porcher
Julie C
JC
Steensma
David P
DP
D016022:Case-Control Studies; D002453:Cell Cycle; D002895:Chromosomes, Human, Pair 5; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D020033:Protein Isoforms; D012322:RNA Precursors; D012326:RNA Splicing; D020687:cdc25 Phosphatases / Q000235:genetics*
D020033:Protein Isoforms; D012322:RNA Precursors; C517009:CDC25C protein, human; D020687:cdc25 Phosphatases