骨髓增生异常综合征患者基因突变情况分析

Gene mutations of patients with myelodysplastic syndromes

目的分析骨髓增生异常综合征（MDS）患者的基因突变情况。方法选择2016年1月至2017年7月中国中医科学院西苑医院初诊的47例MDS患者，采用NGS127．genepanel检测基因突变，分析基因突变与临床特征的关系。结果47例MDS患者中，31例（66．0％）检测到基因突变，涉及有临床意义的突变基因23个，检出率〉5％的基因共7个，由高到低依次为U2AFl（23．4％）、SF381（12．8％）、ASXLl（10．6％）、TET2（8．5％）、BCOR（8．5％）、TP53（8．5％）、DNMT3A（6．4％）。31例基因突变患者中，16例（51．6％）存在2个以上基因协同突变，其中12例患者的协同基因突变存在于不同基因功能组内，高于单一基因功能组内的基因协同突变（4例）。IDH2．KRAS、IDH2．SRSF2、1DH2-STAG2、KRAS-SRSF2、KRAS．STAG2、RUNX1-PHF6、EZH2．ASXLl、EZH2．ZRSR2、NPMl．NRAS基因之间有共存关系（均P〈0．05）。JAK2、KRAS、NRAS、SH283四个信号通路相关的变异等位基因频率（VAF）较低，处于亚克隆地位。1例JAK2突变见于MDS—U患者；1例SH283基因突变见于核型预后极高危患者；2例SETBPl以及2例EZH2突变均见于修订的国际预后评分系统（IPSS．R）预后高危患者。结论MDS患者常见突变基因为U2AFl、SF381、ASXLl、TET2。不同基因功能组内的基因倾向于协同突变。基因突变可用于判断MDS患者预后，作为其治疗的靶点。

Objective To analyze the gene mutations in the patients with myelodysplastic syndromes （MDS）. Methods Forty-seven patients with MDS newly diagnosed in Xiyuan Hospital, China Academy of Chinese Medical Sciences from January 2016 to July 2017 were enrolled. NGS 127-gene panel was used to detect the gene mutations, and the relationship between the gene mutations and the clinicopathological features was also analyzed. Results Thirty-one （66.0 %） cases had gene mutations in 47 patients with MDS, and 23 gene mutations were detected with clinical significauces. There were 7 mutant genes with a mutation frequency over 5 % in the population, including U2AF1 （23.4 %）, SF3BI （12.8 %）, ASXL1 （10.6 %）, TET2 （8.5 %）, BCOR （8.5 %）, TP53 （8.5 %） and DNMT3A （6.4 %） in turn. Among 31 patients with gene mutations, 16 （51.6 %） patients had I〉 2 synergistic mutations, and 12 cases had synergistic mutations in different genetic functional groups, which was higher than that in same genetic functional groups （4 cases）. There was a tendency of coexistence in IDH2-KRAS, IDH2-SRSF2, IDH2-STAG2, KRAS-SRSF2, KRAS-STAG2, RUNX1-PHF6, EZH2-ASXL1, EZH2-ZRSR2, and NPM1-NRAS （all P 〈 0.05）. The variant allele frequency （VAF） of signaling pathway related genes including JAK2, KRAS, NRAS, SH2B3 was low in general and in a sub-clone status. JAK2 gene mutation was observed in 1 case with MDS-U. SH2B3 gene mutation was observed in a patient with very poor prognosis of karyotype. SETPB1 and EZI-I1 gene mutations were observed in two patients with high-risk revised international prognostic scoring system （IPSS-R）. Conclusions The common mutated genes include U2AF1, SF3B1, ASXL1 and TET2. The genes in different genetic functional groups tend to synergistic mutations. Gene mutations can be used to predict the prognosis of diseases and become the target in the treatment of MDS.