Research Project
Grant-in-Aid for Challenging Exploratory Research
Although splicing factor mutations are the most important genetic alterations in MDS, little is known about exact gene targets whose abnormal splicing is responsible for the pathogenesis of MDS. SF3B1 and SRSF2 mutations were associated with distinct clinical phenotypes and outcomes together with RNA splicing. To explore the molecular basis of these distinct features in terms of splicing alterations, RNA sequencing data from SF3B1-mutated and SRSF2-mutated bone marrow hematopoietic cells were compared with those without known splicing factor mutations to detect splicing events significantly enriched in splicing factor mutated cases. SF3B1 mutations caused misrecognition of 3’ splice sites of several genes, which included one of the causative genes for congenital sideroblastic anemia. On the other hand, SRSF2 mutations were characterized by modest but more widespread alterations in exon usage of genes. Our results provide insights into the pathogenesis of splicing factor mutated MDS.
All 2015 2014
All Journal Article (3 results) (of which Peer Reviewed: 3 results, Open Access: 2 results) Presentation (4 results) (of which Invited: 1 results) Book (1 results)
Nature Commun.
Volume: ６ Issue: 1 Pages: 6042-6042
10.1038/ncomms7042
Science
Volume: ３４４ Issue: 6186 Pages: 917-920
10.1126/science.1252328
Leukemia
Volume: (Epub ahead of print) Issue: 9 Pages: 1-7
10.1038/leu.2014.73
