SETD2基因与骨髓增生异常综合征的相关研究

Association of SETD2 gene mutations with myelodysplastic syndrome

目的:探讨SETD2基因与骨髓增生异常综合征(MDS)相关临床预后的关系。方法:应用靶向二代基因测序技术,检测我院180例MDS患者的43个MDS相关基因,并观察SETD2基因对患者原始细胞、血红蛋白、生存时间、无进展生存时间以及治疗效果的影响。结果:180例MDS患者中,我们发现SETD2基因突变包括SETD2 p.L2486R,SETD2 p.E1142G,TET2 p.T2388fs和SETD2 p.F1116fs;单核苷酸多态性包括SETD2 p.M761I,SETD2 p.E639K,SETD2 p.P193L,SETD2 p.M1080I,SETD2 p.N1155K和SETD2 p.P1962L,其中,SETD2 p.M761I,SETD2 p.E639K,SETD2 p.P193L和SETD2 p.M1080I四种SNP位点经预测分析具有危害性和致病性。携带危害性SETD2基因异常的患者共14例,其中同时携带TP53基因突变者占50.0%,同时携带TET基因突变者占28.6%,同时携带ASXL1基因突变者占21.4%。携带SETD2基因异常的MDS患者表现为较高的原始细胞水平(P<0.05);并且单变量和多变量生存分析表明,SETD2基因异常与MDS患者总生存时间和无进展生存时间显著相关(P<0.05)。结论:SETD2基因异常与MDS疾病进展迅速以及不良预后密切相关。

Objective:To investigate the effect of SETD2 gene mutations on clinical features and prognosis in patients with myelodysplastic syndrome(MDS).Method:Next-generation sequencing covering 43 genes was performed using samples from 180 patients with newly diagnosed MDS,and the association of SETD2 variants with blast cells,hemoglobin,overall survival,progression-free survival and the response to treatment was analyzed.Result:In 180 patients with MDS,SETD2 mutations were included p.L2486 R,p.E1142 G,p.T2388 fs and p.F1116 fs.Single nucleotide variants included p.M761 I,p.E639 K,p.P193 L,p.M1080 I,p.N1155 K and p.P1962 L.SETD2 p.M761 I,p.E639 K,p.P193 L and p.M1080 I were predicted to pathogenic SNP using the software tools.Fourteen patients carried the hazardous SETD2 gene variants,and they exhibited a significantly increased frequency of TP53 gene alterations(50.0%),TET2(28.6%)and ASXL1 gene mutations(21.4%).MDS patients with SETD2 gene variants showed higher blast cell counts,in addition(P<0.05).Both univariate and multivariate survival analyses indicated that SETD2 gene variants were significantly associated with poor overall survival and progression-free survival(P<0.05).Conclusion:Our observations show that SETD2 gene variants are associated with rapid progression to leukemia and poor outcomes in patients with MDS.