Genetic landscape of recurrent ASXL1, U2AF1, SF3B1, SRSF2, and EZH2 mutations in 304 Chinese patients with myelodysplastic syndromes
Genetic landscape of recurrent ASXL1, U2AF1, SF3B1, SRSF2, and EZH2 mutations in 304 Chinese patients with myelodysplastic syndromes
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304 例中国骨髓增生异常综合征患者复发 ASXL1、U2AF1、SF3B1、SRSF2 和 EZH2 突变的遗传图谱
DOI：
10.1007/s13277-015-4305-2
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发表时间：
2016-04-01
期刊：
影响因子：
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通讯作者：
Li, Xiao
中科院分区：
文献类型：
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作者：
Wu, Lingyun;Song, Luxi;Li, Xiao
我们确定了中国骨髓增生异常综合征（MDS）患者中5种复发性遗传畸变的生物学和预后意义。共304例中国MDS患者使用下一代测序技术筛查5个基因（ASXL 1、U2 AF 1、SF 3B 1、SRSF 2和EZH 2）的已知突变。其中，97名患者（31.9%）在5个基因中至少有一个突变，并且这些突变的患者具有不同的临床特征。ASXL 1、U2 AF 1、SF 3B 1、SRSF 2和EZH 2突变的发生率分别为11.8%、8.6%、8.2%、4.3%和3.6%。U2 AF 1、SRSF 2和EZH 2突变患者的高风险亚型比低风险亚型更常见，而SF 3B 1突变经常在MDS亚型中证实，环形铁粒幼细胞增加。ASXL 1突变的病例具有较高比例的复杂核型，而U2 AF 1突变在8三体或20 q缺失的患者中更常见。值得注意的是，在124例正常核型的患者中，48例（38.7%）至少有一个突变。与未发生U2 AF 1或SRSF 2突变的患者相比，发生U2 AF 1或SRSF 2突变的患者的总生存期（OS）时间显著缩短（U2 AF 1突变：中位OS分别为18 vs 54个月，p = 0.032; SRSF 2突变：中位OS分别为11 vs 54个月，p = 0.005）。多变量分析显示，SRSF 2突变的存在是OS的独立不利预后因素（风险比2.039; 95%置信区间1.040-4.000; p = 0.038）。这些数据表明表观遗传修饰和剪接体基因突变在中国MDS患者中很常见，而U2 AF 1和SRSF 2突变似乎预示着不良预后。
We determined the biological and prognostic significance of five recurrent genetic aberrations in Chinese patients with myelodysplastic syndromes (MDS). A total of 304 Chinese MDS patients were screened for known mutations in five genes (ASXL1, U2AF1, SF3B1, SRSF2, and EZH2) using next-generation sequencing. Of these, 97 patients (31.9 %) harbored at least one mutation in the five genes, and patients harboring these mutations had distinct clinical features. Incidence ratios for mutations in ASXL1, U2AF1, SF3B1, SRSF2, and EZH2 were 11.8, 8.6, 8.2, 4.3, and 3.6 %, respectively. Patients with U2AF1, SRSF2, and EZH2 mutations more commonly had high-risk than low-risk subtypes, while SF3B1 mutations were frequently confirmed in MDS subtypes with increased ring sideroblasts. Cases with ASXL1 mutations had a higher percentage of complex karyotypes, while U2AF1 mutations were more common in patients with trisomy 8 or 20q deletions. Notably, among 124 patients with a normal karyotype, 48 (38.7 %) had at least one mutation. Patients with U2AF1 or SRSF2 mutations had significantly shorter overall survival (OS) times compared with patients without these mutations (U2AF1 mutations: median OS, 18 vs 54 months, p = 0.032; SRSF2 mutations: median OS 11 vs 54 months, p = 0.005, respectively). Multivariate analysis showed that the presence of SRSF2 mutations was an independent unfavorable prognostic factor for OS (hazard ratio 2.039; 95 % confidence interval 1.040-4.000; p = 0.038). These data suggest that mutations in epigenetic modification and splicesome genes are common in Chinese patients with MDS, while mutations in U2AF1 and SRSF2 appear to predict an unfavorable prognosis.