摘要
目的:探讨骨髓增生异常综合征(myelodysplastic syndromes,MDS)患者15种常见突变基因的突变规律及相关临床意义。方法:选取初诊MDS和MDS转化的急性髓系白血病(acute myeloid leukemia,AML)患者共97例。DNA测序检测并分析患者骨髓样本中15种基因的突变,包括RNA剪接因子基因U2AF1,SF3B1和SRSF2,表观遗传调节基因ASXL1,DNMT3A,IDH1,IDH2和TET2,信号转导通路基因JAK2,NRAS,KRAS和PTPN11,以及TP53,RUNX1和SETBP1。结果:67.98%的患者上述基因突变阳性,23.71%的患者同时携带多个基因突变,共检测到18种不同突变的组合。U2AF1突变最多见,其次为ASXL1和TP53突变。ASXL1和RUNX1突变常伴随其他基因突变,而SF3B1突变常单独出现。RNA剪接因子类基因突变互斥,常与表观遗传调节类基因突变相伴随。MDS/AML患者基因突变阳性率高于初诊MDS患者(85.71%vs 60.52%,P=0.038)。基因突变阳性组年龄显著大于突变阴性组,同时成人组基因突变阳性率高于儿童和青少年组,差异均有统计学意义(P=0.003)。结论:MDS及MDS/AML患者中常见基因突变的组合具有一定规律,与基因的功能分类和患者的年龄有关。
Objective： To investigate the mutaome profile of the 15 common mutated genes and related clinical significance in patients with myelodysplastic syndromes（MDS）. Methods： Ninety-seven patients primarily diagnosed as MDS and MDS progressed to acute myeloid leukemia（MDS/AML） were enrolled. Mutated genes were analyzed in bone marrow samples by Sanger sequencing, including the RNA splicing factor genes U2 AF1, SF3 B1 and SRSF2, epigenetic regulation genes ASXL1, DNMT3 A, IDH1, IDH2 and TET2, signal transduction pathway genes JAK2, NRAS, KRAS, PTPN11, as well as other genes TP53, RUNX1 and SETBP1. Results： Mutations were detected in 67.98% of the patients, 23.71% carried mutations of multiple genes, and a total of 18 combinations of different mutations were detected. U2 AF1 was the most commonly mutated gene, followed by ASXL1 and TP53. ASXL1 and RUNX1 mutations are often concomitant with other gene mutations, while SF3 B1 mutations usually occurred alone. RNA splicing factor genes were mutually exclusive, and they are more likely accompanied by mutation of epigenetic regulation genes. The genes mutation frequency in primarily diagnosed MDS/AML patients was significantly higher than that in MDS patients（85.71% vs 60.52%, P=0.038）. The age in mutation positive group was higher than that of mutation negative group, the frequency of gene mutation in adult group was higher than that of children and adolescent group, the differences were all statistically significant（P=0.003）. Conclusion： There were certain rules in the mutaome profile of MDS and MDS/AML patients, which was related to gene function and age of patients.
出处
《临床与病理杂志》
2017年第11期2332-2338,共7页
Journal of Clinical and Pathological Research
基金
山东省自然科学基金(ZR2016HP02)~~
