title: Mutational analysis of splicing machinery genes SF3B1, U2AF1 and SRSF2 in myelodysplasia and other common tumors.
abstract: Recurrent somatic mutations in splicing machinery components, including SF3B1, U2AF1 and SRSF2 genes have recently been reported in myelodysplastic syndromes (MDS). Such a recurrent nature strongly suggests that these mutations play important roles in tumor development. To see whether SF3B1, U2AF1 and SRSF2 mutations occur in other human tumors besides MDS, we analyzed the hotspot mutation regions of these genes in 2,345 tumor tissues from various origins (61 MDS, other 616 hematologic tumors, 1,421 epithelial tumors and 247 non-epithelial stromal tumors) by single-strand conformation polymorphism analysis. We found SF3B1, U2AF1 and SRSF2 mutations in 5 (8.2%), 12 (19.7%) and 8 (13.1%) of 61 MDS, respectively. We also confirmed these mutations in other myeloid neoplasia, including de novo acute myelogenous leukemia (AML), chronic myelomonocytic leukemia and MDS/myeloproliferative disorder. In addition, we discovered that the SRSF2 gene was mutated in two childhood acute lymphoblastic leukemias (childhood ALL) (1.5%). In solid tumors, we found SF3B1 mutations in gastric and prostate cancers, and U2AF1 mutation in a borderline mucinous tumor of ovary, but the overall incidences of the hotspot mutation regions were very low (0.2%). Our data suggest that SF3B1, U2AF1 and SRSF2 mutations occur not only in myeloid lineage tumors but also in lymphoid lineage tumors. The data suggest that the splicing gene mutations play important roles in the pathogenesis of hematologic tumors, but rarely in solid tumors.
authors.affiliation: Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, 137-701, Korea.
authors.forename: Eun Mi
authors.initials: EM
authors.lastname: Je
authors.forename: Nam Jin
authors.initials: NJ
authors.lastname: Yoo
authors.forename: Yoo Jin
authors.initials: YJ
authors.lastname: Kim
authors.forename: Myung Shin
authors.initials: MS
authors.lastname: Kim
authors.forename: Sug Hyung
authors.initials: SH
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People; D004252:DNA Mutational Analysis; D005260:Female; D019337:Hematologic Neoplasms / Q000235:genetics; D006801:Humans; D007723:Korea; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000235:genetics; D054437:Myelodysplastic-Myeloproliferative Diseases / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics*; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics*; D010750:Phosphoproteins / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D012326:RNA Splicing; D000072260:RNA Splicing Factors; D017413:Ribonucleoprotein, U2 Small Nuclear / Q000235:genetics*; D012261:Ribonucleoproteins / Q000235:genetics*; D000068103:Serine-Arginine Splicing Factors; D000072668:Splicing Factor U2AF
chemical_list: D009687:Nuclear Proteins; D010750:Phosphoproteins; D000072260:RNA Splicing Factors; D017413:Ribonucleoprotein, U2 Small Nuclear; D012261:Ribonucleoproteins; C112491:SF3B1 protein, human; D000072668:Splicing Factor U2AF; C076753:U2AF1 protein, human; C073288:SRSF2 protein, human; D000068103:Serine-Arginine Splicing Factors