The Expression And Significance Of Gene Mutations In Myelodysplastic Syndrome

Objective:To investigate the expression and significance of gene mutation in Myelodysplastic syndrome.Methods:From January 2015 to October 2017,76 patients with MDS diagnosed in Department of Hematology of First Affiliated Hospital of Shihezi University and Department of Hematology of People's Hospital of Xinjiang Uygur Autonomous Region were enrolled.All patients underwent examinations of blood routine,morphological examination of bone marrow and peripheral blood,bone marrow biopsy,immunophenotyping,cytogenetics genetics,molecular genetics and so on,furthermore gene mutations were detected by using PCR and direct sequencing.Using SPSS 19.0 statistical software,the measurement data were tested by non-parametricrank sum test,Whitney U test.The chi-square test was used for counting data.Spearman method applied to the correlation analysis.Bilateral P<0.05 was considered statistically significant.Results:1.There were as followed,U2AF1(25.0%,5/20),TET2(21.2%,15/71),SF3B1(9.1%,4/44),TP53(8.8%,3/34),DNMT3A(8.3%,6/72),ASXL1(5.6%,4/72),BCOR(5.0%,1/20),NPM1(3.8%,1/26),IDH1(3.3%,2/60)),IDH2(3.3%,2/60),JAK2(3.0%,1/33),ETV6(2.9%,1/34),EZH2(1.7%,1/59),RUNX1(0.0%,0/45)),CBL(0.0%,0/33),NRAS(0.0%,0/33),SRSF2(0.0%,0/46),ZRSR2(0.0%,0/20),FLT3-ITD(0.0%,0/26),CEBPA(0.0%,0/26)and C-KIT(0.0%,0/26),which were sorted by the frequency of gene mutation.2.There was a statistically significant difference in age between the TET2 mutation group and the TET2 non-mutation group(P=0.034),the TET2 mutation group was older(71 years old vs 56.5 years old),and there was no significant difference in sex,white blood cell count,neutrophil count,hemoglobin,platelet count,ratio of bone marrow blast cell and karyotype between the two groups(P>0.05);There were no statistics in sex,age,white blood cell count,neutrophil count,hemoglobin,platelet count,ratio of bone marrow blast cells and karyotype in the mutation and non-mutation groups of DNMT3 A,IDH1/2,ASXL1,U2AF1 and TP53 mutations(P>0.05).3.DNMT3 A was lowly correlated with SF3B1(r=0.311,P=0.040);U2AF1 was moderately correlated with +8(r=0.577,P=0.008);TP53 was highly correlated with complex karyotype(r=0.804,P<0.001),and moderately correlated with JAK2(r=0.559,P=0.001);JAK2 was moderately associated with complex karyotypes(r=0.696,P<0.001);The correlation between 7q-and 20q-was very weak(r=0.288,P=0.012).4.There was no significant difference in the distribution of TET2,DNMT3 A,IDH1/2,SF3B1,U2AF1,ASXL1 and TP53 mutation in the subtype of myelodysplastic syndrome in WHO(2008)(P>0.05).5.There were no significant differences in the distribution of TET2,DNMT3 A,IDH1/2,SF3B1,U2AF1,ASXL1 and TP53 mutation in the subgroup of WPSS,IPSS and IPSS-R prognostic score systems of myelodysplastic syndromes(P>0.05).According to the WPSS,IPSS and IPSS-R prognostic scoringsystem,patients were divided into relatively low-risk groups(WPSS very low-risk group,low-risk group and intermediate-risk group,IPSS low-risk group and intermediate-risk 1 group,IPSS-R very low-risk group,low risk group and intermediate-risk group)and relatively high risk group(WPSS high-risk group and very high-risk group,IPSS intermediate-risk 2 group and high-risk group,IPSS-R intermediate-risk group,high-risk group and very high-risk group),there was no significant difference in distribution of all tested gene mutations in the relatively low-risk groups and relatively high-risk groups of WPSS and IPSS(P>0.05);There was significant difference in the frequency of U2AF1 mutation in the relatively low-risk groups and relatively high-risk groups of IPSS-R(P=0.038),and no significant difference in the distribution of other gene mutations between the two group(P>0.05).6.The detection rate of abnormal karyotype analysis was 43.4%(33/76),the detection rate of positive mutation of gene mutation detection was 44.7%(34/76),and the detection rate of abnormal genetics of the combined detections of the two was 71.1%(54/76),there was a statistically significant difference in the detection rate of abnormal genetics of the three detections(c2=14.828,P=0.001).Conclusions:1.Gene mutations involving in DNA methylation,RNA splicing,DNA repair and chromatin modification are more frequent in MDS,and there are certain differences compared with the frequency of domestic and foreign gene mutations.2.Those with TET2 mutations are older than those without TET2 mutations.3.There is a certain correlation between gene mutations and karyotypes,and the combined detections of these two helps to increase the detection rate of abnormal genetics and helps to predict the prognosis.