Analysis Of Gene Mutation In Patients With Myelodysplastic Syndrome

ObjectiveThe second generation sequencing technology was used to detect the gene mutation of MDS patients,and the differences of gene mutation rate,gender,age,IPSS-R were analyzed to explore the correlation between them.Materials and MethodA retrospective analysis was made of 118 MDS patients with gene mutation detected in Henan cancer hospital from June 2016 to may 2019,including 69 males and 49 females,with a median age of 53(14-89)years.According to the consensus of Chinese experts on diagnosis and treatment of MDS(2019 version),diagnosis and classification were carried out.Among them,10 cases(8%)had MDS with monocyte dysplasia(mds-sld),35 cases(30%)had MDS with multicellular dysplasia(mds-mld),22 cases(19%)had MDS with annular sideroblastic erythrocytes(mds-rs)and 51 cases(43%)had MDS with primitive cell increase(mds-eb).According to the modified international prognostic score system(IPSS-R),8 cases were in the extremely low risk group(7%),22 cases in the low risk group(19%),41 cases in the medium risk group(35%),30 cases in the high risk group(25%),17 cases in the extremely high risk group(14%).The median leukocyte count was 2.68×109/L[(0.4-36.59)×109/L],the median neutrophil count was 1.32×109/L[(0.1-29.52)/109/L],the median hemoglobin content was 74 g/L(24-126 g/L),and the median platelet count was 60×109/L[(5-392)×109/L.Second generation sequencing technology was used to detect gene mutations in patients.Result1.The average number of mutation genes in 118 patients was 1.94.Among them,45.7%patients carried one mutation gene(54/118),32.2%patients carried two mutations(38/118),11.9%patients carried three mutations(14/118),4.2%patients carried four mutations(5/118),4.2%patients carried five mutations(5/11 8),1.7%patients carried six mutations(6/118).There were 64 patients(54.2%of the total)with more than two mutations,and the average number of mutations was 2.73.Among all patients,the first six genes with the highest mutation detection rate were:U2AF1(32.2%,38/118),TET2(32.2%,38/118),ASXL1(13.6%,16/118),RUNX1(11.9%,14/118),TP53(9.3%,11/118),CBL(6.8%,8/118).2.71 cases were younger than 60,47 cases were older than 60.There were 1.41 Mutation Genes in the group of<60 years old,2.53 in the group of>60 years old,with no statistical significance;Runx1 in the group of<60 years old(4 cases,5.6%),with statistical significance compared with that in the group of>60 years old(10 cases,21.3%)(P=0.018).There was no statistical difference among the age groups of the other mutant genes.3.8 cases(7%)in the extremely low risk group,with an average of 1.25;22 cases(19%)in the low risk group,with an average of 1.77;41 cases(35%)in the medium risk group,with an average of 1.88;30 cases(25%)in the high risk group,with an average of 2.3;17 cases(14%)in the extremely high risk group,with an average of 2.0.Scores ≤3.0,i.e.very low-risk and low-risk groups,30 cases in total.with an average number of mutations of 1.53;scores ≥ 3.5,i.e.medium risk,high-risk and very high-risk groups,88 cases in total,with an average number of mutations of 2.05;MDS patients with high ipss-r scores had significantly more average mutation genes than those with low scores(P=0.04).SF3B1 in patients with score ≤3.0(4 cases,13.3%)was significantly higher than that in patients with score≥ 3.5(2 cases,2.3%%).The difference was statistically significant(P=0.036).4.There were more mutations of TP53 in MDS patients with normal platelets,and the difference was statistically significant(P=0.004).There were more mutations in CBL in MDS patients with hemoglobin≥80×109/L,and the difference was statistically significant(P=0.038).5.Univariate/multivariate COX regression analysis revealed that RUNX1 and TP53 were independent risk factors for poor prognosis in MDS patients.ConclusionRUNX1 and TP53 gene indicates that the prognosis of MDS patients is poor,and the mutation rate is high in the elderly patients,which has no significant correlation with ipss-r score;sf3b1 gene mutations are more common in MDS patients with better prognosis,without age difference,the more co mutations,the higher the prognosis score.The detection of gene mutation based on second-generation sequencing provides a powerful supplement for the prognosis score of MDS.In-depth study of the impact of CO mutation on the pathogenesis,development and prognosis of MDS will provide a new idea for the treatment of MDS.