Clinical features and biological implications of different U2AF1 mutation types in myelodysplastic syndromes

• Published in: Genes chromosomes & cancer Vol. 57; no. 2; pp. 80 - 88
• Main Authors: Li, Bing, Liu, Jinqin, Jia, Yujiao, Wang, Jingya, Xu, Zefeng, Qin, Tiejun, Shi, Zhongxun, Song, Zhen, Peng, Shuailing, Huang, Huijun, Fang, Liwei, Zhang, Hongli, Pan, Lijuan, Hu, Naibo, Qu, Shiqiang, Zhang, Yue, Wu, Jian, Liu, Na, Ru, Kun, Huang, Gang, Xiao, Zhijian
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.02.2018
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Cohort Studies; DNA Mutational Analysis - methods; Female; Fibrosis; Hemoglobin; High-Throughput Nucleotide Sequencing - methods; Humans; Karyotypes; Male; Middle Aged; Mutation; Mutation - genetics; Myelodysplastic syndrome; Myelodysplastic syndromes; Myelodysplastic Syndromes - genetics; Myelodysplastic Syndromes - metabolism; Prognosis; Sequence Analysis, DNA - methods; Sideroblasts; Splicing Factor U2AF - genetics; Splicing Factor U2AF - metabolism; Thrombocytopenia
• ISSN: 1045-2257; 1098-2264; 1098-2264
• DOI: 10.1002/gcc.22510

U2AF1 mutations (U2AF1MT) occur commonly in myelodysplastic syndromes (MDS) without ring sideroblasts. The aim of this study was to investigate the clinical and biological implications of different U2AF1 mutation types in MDS. We performed targeted gene sequencing in a cohort of 511 MDS patients. Eighty‐six patients (17%) were found to have U2AF1MT, which occurred more common in younger patients (P = .001) and represented ancestral lesions in a substantial proportion (71%) of cases. ASXL1MT and isolated +8 were significantly enriched in U2AF1MT‐positive cases, whereas TP53MT, SF3B1MT, and complex karyotypes were inversely associated with U2AF1MT. U2AFS34 subjects were enriched for isolated +8 and were inversely associated with complex karyotypes. U2AF1MT was significantly associated with anemia, thrombocytopenia, and poor survival in both lower‐risk and higher‐risk MDS. U2AF1S34 subjects had more frequently platelet levels of <50 × 109/L (P = .043) and U2AF1Q157/U2AF1R156 subjects had more frequently hemoglobin concentrations at <80 g/L (P = .008) and more often overt fibrosis (P = .049). In conclusion, our study indicates that U2AF1MT is one of the earliest genetic events in MDS patients and that different types of U2AF1MT have distinct clinical and biological characteristics.