title: Clinical implications of U2AF1 mutation in patients with myelodysplastic syndrome and its stability during disease progression.
abstract: We aimed to analyze clinical impacts of the U2AF1 mutation on patients with myelodysplastic syndrome (MDS) and its stability during disease progression. We checked mutation status of the U2AF1 by direct sequencing in 478 de novo MDS patients and correlated with the clinical characteristics and outcomes. We also sequentially analyzed the U2AF1 mutation in 421 samples from 142 patients to determine its stability during the disease courses. Thirty-six patients (7.5%) were found to have U2AF1 mutations, which occurred more frequently in younger patients (P = 0.033). U2AF1 mutation was an independent poor-risk factor for overall survival (OS) in all patients (P = 0.030) and younger patients (P = 0.041). U2AF1 mutation could also predict shorter time-to-leukemia transformation (TTL) in younger patients (P = 0.020). In addition, U2AF1 mutation was associated with shorter TTL in lower-risk MDS patients. Sequential analyses showed all original U2AF1 mutations in U2AF1-mutated patients were retained during follow-ups unless complete remission was achieved, whereas none of the U2AF1-wild patients acquired a novel mutation during disease evolution. U2AF1 mutation is more prevalent in younger MDS patients and associated with inferior outcomes although it is stable during the clinical course. The mutation may be used as a biomarker for risk stratification.
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: Jih-Luh
authors.initials: JL
authors.lastname: Tang
authors.forename: Chien-Ting
authors.initials: CT
authors.lastname: Lin
authors.forename: Yuan-Yeh
authors.initials: YY
authors.lastname: Kuo
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: Yen-Jun
authors.initials: YJ
authors.lastname: Lai
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: Hsin-An
authors.initials: HA
authors.lastname: Hou
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: Woei
authors.initials: W
authors.lastname: Tsay
authors.forename: Hwei-Fang
authors.initials: HF
authors.lastname: Tien
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D002471:Cell Transformation, Neoplastic; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D056726:Genetic Association Studies; D006801:Humans; D007938:Leukemia / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D012261:Ribonucleoproteins / Q000235:genetics* / Q000378:metabolism; D000072668:Splicing Factor U2AF; D016019:Survival Analysis; D013624:Taiwan; D055815:Young Adult
chemical_list: D009687:Nuclear Proteins; D012261:Ribonucleoproteins; D000072668:Splicing Factor U2AF; C076753:U2AF1 protein, human