title: The clinical implication of SRSF2 mutation in patients with myelodysplastic syndrome and its stability during disease evolution.
abstract: Recurrent somatic mutation of SRSF2, one of the RNA splicing machinery genes, has been identified in a substantial proportion of patients with myelodysplastic syndrome (MDS). However, the clinical and biologic characteristics of MDS with this mutation remain to be addressed. In this study, 34 (14.6%) of the 233 MDS patients were found to have SRSF2 mutation. SRSF2 mutation was closely associated with male sex (P = .001) and older age (P < .001). It occurred concurrently with at least 1 additional mutation in 29 patients (85.3%) and was closely associated with RUNX1, IDH2, and ASXL1 mutations (P = .004, P < .001, and P < .001, respectively). Patients with SRSF2 mutation had an inferior overall survival (P = .010), especially in the lower risk patients. Further exploration showed that the prognostic impact of SRSF2 mutation might be attributed to its close association with old age. Sequential analyses in 173 samples from 66 patients showed that all SRSF2-mutated patients retained their original mutations, whereas none of the SRSF2-wild patients acquired a novel mutation during disease evolution. In conclusion, SRSF2 mutation is associated with distinct clinical and biologic features in MDS patients. It is stable during the clinical course and may play little role in disease progression.
authors.affiliation: Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Shang-Ju
authors.initials: SJ
authors.lastname: Wu
authors.forename: Yuan-Yeh
authors.initials: YY
authors.lastname: Kuo
authors.forename: Hsin-An
authors.initials: HA
authors.lastname: Hou
authors.forename: Li-Yu
authors.initials: LY
authors.lastname: Li
authors.forename: Mei-Hsuan
authors.initials: MH
authors.lastname: Tseng
authors.forename: Chi-Fei
authors.initials: CF
authors.lastname: Huang
authors.forename: Fen-Yu
authors.initials: FY
authors.lastname: Lee
authors.forename: Ming-Chih
authors.initials: MC
authors.lastname: Liu
authors.forename: Chia-Wen
authors.initials: CW
authors.lastname: Liu
authors.forename: Chien-Ting
authors.initials: CT
authors.lastname: Lin
authors.forename: Chien-Yuan
authors.initials: CY
authors.lastname: Chen
authors.forename: Wen-Chien
authors.initials: WC
authors.lastname: Chou
authors.forename: Ming
authors.initials: M
authors.lastname: Yao
authors.forename: Shang-Yi
authors.initials: SY
authors.lastname: Huang
authors.forename: Bor-Sheng
authors.initials: BS
authors.lastname: Ko
authors.forename: Jih-Luh
authors.initials: JL
authors.lastname: Tang
authors.forename: Woei
authors.initials: W
authors.lastname: Tsay
authors.forename: Hwei-Fang
authors.initials: HF
authors.lastname: Tien
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics*; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D050505:Mutant Proteins / Q000737:chemistry* / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000401:mortality; D009687:Nuclear Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012097:Repressor Proteins / Q000235:genetics*; D012261:Ribonucleoproteins / Q000235:genetics*; D000068103:Serine-Arginine Splicing Factors; D015996:Survival Rate; D055815:Young Adult
chemical_list: C473949:ASXL1 protein, human; D050676:Core Binding Factor Alpha 2 Subunit; D050505:Mutant Proteins; D009687:Nuclear Proteins; C493728:RUNX1 protein, human; D012097:Repressor Proteins; D012261:Ribonucleoproteins; C073288:SRSF2 protein, human; D000068103:Serine-Arginine Splicing Factors; C538784:IDH2 protein, human; D007521:Isocitrate Dehydrogenase