title: IDH mutations are closely associated with mutations of DNMT3A, ASXL1 and SRSF2 in patients with myelodysplastic syndromes and are stable during disease evolution.
abstract: Current information about clinical significance of IDH mutations in myelodysplastic syndromes (MDS), their association with other genetic alterations and the stability during disease progression is limited. In this study, IDH mutations were identified in 4.6% of 477 patients with MDS based on the FAB classification and in 2.2 % of 368 patients based on the 2008 WHO classification. IDH mutations were closely associated with older age, higher platelet counts, and mutations of DNMT3A (36.4% vs. 8.7%, P < 0.001), ASXL1 (47.6% vs. 22.0%, P = 0.007), and SRSF2 (45.5% vs. 11.8%, P < 0.001). IDH2 mutation was a poor prognostic factor for overall survival in patients with lower-risk MDS, based on international prognosis scoring system (IPSS), FAB classification, WHO classification, or revised IPSS (all P ≦ 0.001), but not in higher-risk groups. Sequential studies in 151 patients demonstrated that all IDH-mutated patients retained the same mutation during disease evolution while none of the IDH-wild patients acquired a novel mutation during follow-ups. In conclusion, IDH mutation is a useful biomarker for risk stratification of patients with lower-risk MDS. IDH mutations are stable during the clinical course. The mutation, in association with other genetic alterations, may play a role in the development, but not progression of MDS.
authors.affiliation: Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Chien-Chin
authors.initials: CC
authors.lastname: Lin
authors.forename: Hsin-An
authors.initials: HA
authors.lastname: Hou
authors.forename: Wen-Chien
authors.initials: WC
authors.lastname: Chou
authors.forename: Yuan-Yeh
authors.initials: YY
authors.lastname: Kuo
authors.forename: Chieh-Yu
authors.initials: CY
authors.lastname: Liu
authors.forename: Chien-Yuan
authors.initials: CY
authors.lastname: Chen
authors.forename: Yan-Jun
authors.initials: YJ
authors.lastname: Lai
authors.forename: Mei-Hsuan
authors.initials: MH
authors.lastname: Tseng
authors.forename: Chi-Fei
authors.initials: CF
authors.lastname: Huang
authors.forename: Ying-Chieh
authors.initials: YC
authors.lastname: Chiang
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: Jih-Luh
authors.initials: JL
authors.lastname: Tang
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: Shang-Ju
authors.initials: SJ
authors.lastname: Wu
authors.forename: Woei
authors.initials: W
authors.lastname: Tsay
authors.forename: Yao-Chang
authors.initials: YC
authors.lastname: Chen
authors.forename: Hwei-Fang
authors.initials: HF
authors.lastname: Tien
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002869:Chromosome Aberrations; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics*; D000090205:DNA Methyltransferase 3A; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D059785:Karyotype; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D009687:Nuclear Proteins / Q000235:genetics*; D063868:Patient Outcome Assessment; D011379:Prognosis; D012097:Repressor Proteins / Q000235:genetics*; D012261:Ribonucleoproteins / Q000235:genetics*; D017422:Sequence Analysis, DNA; D000068103:Serine-Arginine Splicing Factors; D055815:Young Adult
chemical_list: C473949:ASXL1 protein, human; C000717967:DNMT3A protein, human; D009687:Nuclear Proteins; D012097:Repressor Proteins; D012261:Ribonucleoproteins; C073288:SRSF2 protein, human; D000068103:Serine-Arginine Splicing Factors; C538784:IDH2 protein, human; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A