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. 2018 Feb;57(2):80-88.
doi: 10.1002/gcc.22510. Epub 2017 Nov 23.

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

Bing Li  1   2 , Jinqin Liu  2 , Yujiao Jia  3 , Jingya Wang  1 , Zefeng Xu  1   2 , Tiejun Qin  1 , Zhongxun Shi  1 , Zhen Song  4 , Shuailing Peng  1 , Huijun Huang  1 , Liwei Fang  1 , Hongli Zhang  1 , Lijuan Pan  1 , Naibo Hu  1 , Shiqiang Qu  1 , Yue Zhang  1   2 , Jian Wu  5 , Na Liu  5 , Kun Ru  3 , Gang Huang  6 , Zhijian Xiao  1   2
Affiliations

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

Bing Li et al. Genes Chromosomes Cancer. 2018 Feb.

Abstract

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.

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Figures

FIGURE 1
FIGURE 1
Karyotypes and mutated genes in MDS. (A) Frequency of abnormal karyotypes in 511 cases. (B) Frequency of 43 significantly mutated genes (>1%) in 511 patients with different WHO subtypes, as indicated with different colors
FIGURE 2
FIGURE 2
Clinical characteristic of patients with U2AF1MT. (A) The percentage of U2AF1MT in different age group. (B) The hemoglobin and platelet level in the U2AF1MT and U2AF1WT groups. (C) The percentage of U2AF1MT in lower-risk and higher-risk groups. Longer blue lines in (B) indicate median and shorter blue lines indicate interquartile range
FIGURE 3
FIGURE 3
Most and least frequently co-occurring gene mutations and abnormal karyotypes in U2AF1MT patients. (A) Prevalence of co-occurring gene mutations and abnormal karyotypes in U2AF1MT subjects compared with U2AF1WT subjects, using univariate analysis. (B) Odds ratios of significant co-occurring gene mutations and abnormal karyotypes in U2AF1MT subjects in multivariate analysis. (C) Prevalence of co-occurring gene mutations in subjects with different types of U2AF1MT. * indicates no sample; S34 indicates U2AF1S34; Q157/R156 indicates U2AF1Q157/U2AF1R156; and U2AF1WT indicates U2AF1 wild type
FIGURE 4
FIGURE 4
Clinical characteristic of patients with different types of U2AF1MT. The association between U2AF1S34 or U2AF1Q157/U2AF1R156 and thrombocytopenia (A), anemia (B), myelofibrosis (C), isolated +8, and complex karyotype (D), and lower-and higher-risk groups (E). S34 indicates U2AF1S34; Q157/R156 indicates U2AF1Q157/U2AF1R156; and U2AF1WT indicates U2AF1 wild type
FIGURE 5
FIGURE 5
Analysis of clonal architecture of U2AF1-mutated cases. Variant allele fractions (VAF) of gene mutations identified in three representative patients with U2AF1 mutations. According to the statistically significant differences in observed VAF among gene mutations, the U2AF1 mutation is classified as ancestral in (A) and (B) and as subclonal (C). Gene mutation clearance observed in five U2AF1MT patients who received single-agent decitabine treatment (D-H). The VAF (left y-axis) and percentage of BM blasts (right y-axis) are indicated across time points (x-axis)
FIGURE 6
FIGURE 6
Overall survival in patients with U2AF1 mutations. (A) Survival curves of U2AF1MT patients. (B) and (C) Subset survival analyses of U2AF1MT patients in lower-risk and higher-risk groups. (D) Survival curves of U2AF1MT patients stratified as ancestral or subclonal groups. (E) and (F) Subset survival analyses of U2AF1MT patients stratified as ancestral or subclonal groups in lower-risk and higher-risk groups. (G) Survival curves of U2AF1MT patients stratified as U2AF1S34 or U2AF1Q157/U2AF1R156. (H) and (I) Subset survival analyses of U2AF1MT patients stratified as U2AF1S34 or U2AF1Q157/U2AF1R156 in lower-risk and higher-risk groups
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References

    1. Chamseddine AN, Jabbour E, Kantarjian HM, Bohannan ZS, Garcia-Manero G. Unraveling myelodysplastic syndromes: current knowledge and future directions. Curr Oncol Rep. 2016;18:4. - PubMed
    1. Haider M, Duncavage EJ, Afaneh KF, Bejar R, List AF. New insight into the biology, risk stratification, and targeted treatment of myelodysplastic syndromes. AM Soc Clin Oncol Educ Book. 2017;37:480–494. - PubMed
    1. Della Porta MG, Gallì A, Bacigalupo A, et al. Clinical effects of driver somatic mutations on the outcomes of patients with myelodysplasbiolog-icalbiologicaltic syndromes treated with allogenetic hematopoietic stem-cell transplantation. J Clin Oncol. 2016;34:3627–3637. - PMC - PubMed
    1. Bejar R, Stevenson K, Abdel-Wahab O, et al. Clinical effect of point mutations in myelodysplastic syndromes. N Engl J Med. 2011;364:2496–2506. - PMC - PubMed
    1. Papaemmanuil E, Gerstung M, Malcovati L, et al. Clinical and biolog myelodysplasticical implications of driver mutations in myelodysplastic syndromes. Blood. 2013;122:3616–3627. - PMC - PubMed

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