Identification of mutated splicing factor target genes

2015 Fiscal Year Final Research Report

• Project/Area Number: 26640075
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology
• Research Institution: National Hospital Organization Nagoya Medical Center (2015); Kyoto University (2014)
• Principal Investigator: SANADA MASASHI 独立行政法人国立病院機構(名古屋医療センター臨床研究センター), その他部局等, その他 (20529044)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: 骨髄異形成症候群 / MDS / RNAスプライシング / RNAシーケンス

Outline of Final Research Achievements

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.

Free Research Field

血液腫瘍学