Combined Detection And Analysis Of 51 Kinds Of Gene Mutations In Myelodysplastic Syndromes With Trisomy 8 Abnormality

Objectives To investigate the mutational profiles of myelodysplastic syndromes(MDS)patients with trisomy 8 abnormality and analyze the characteristics of mutational profiles for correlations with clinical features,which might contribute to detect the pathogenesis of MDS with trisomy 8 abnormality and help to increase the accuracy of diagnosis and risk evaluation.Methods A total of 122 patients with MDS diagnosed and treated in the First Affiliated Hospital of Soochow University between January 2016 and January 2018 were reviewed.P-values<0.05 were considered statistically significant.Results1.A total of 243 candidate mutations were found in 39 kinds of genes.Overall,100 of122 patients(81.9%)harbored at least one mutation.The number of mutations per patient ranged from 0-6(median 2).The most frequently mutated genes were as follows:U2AF1(31,25.4%)?ASXL1(26,21.3%)?RUNX1(19,15.5%)?TET2(13,10.6%)?NRAS(11,9.0%)?DNMT3A(11,9.0%)?BCOR(11,9.0%)?SETBP1(10,8.1%)?NPM1(9,7.3%)?SRSF2(8,6.5%)?CSMD1(8,6.5%)?TP53(7,5.7%)?SF3B1(7,5.7%).2.24 of 27 patients with trisomy 8 abnormality harbored at least one mutation.The number of mutations were not significant compared with the patients without trisomy 8.The frequencies of mutations of genes associated to RNA splicing were strongly higher in MDS with trisomy 8(P=0.001).The mean variant allele fraction(VAF)of U2AF1 was41.24%(range,30.1%-47.1%).A Mann-Whitney U test was run to determine if there were differences in VAF between MDS with trisomy 8 and without trisomy 8.VAF for MDS with trisomy 8(mean rank=19.80)and MDS without trisomy 8(mean rank=12.44)were statistically significantly different,U=145,z=-1.488,p=.142.Distributions of the VAF for two groups were not similar.and VAF of MDS with trisomy 8 were higher.3.The frequencies of U2AF1 mutations were significantly higher in MDS with trisomy 8,compared to MDS without trisomy 8(?~2=15.206,P=0.001).4.Among the 31 U2AF1-mutated patients,3 substitution mutations were found:17cases with S34 Y mutation,in which one case also had Q157 R mutation;14 cases with S34 F mutation.The distributions of S34 Y and S34 F did not have significant difference between MDS with trisomy 8 and without trisomy 8.5.The clinical characteristics of 27 cases with trisomy 8 were analyzed,compared with 63 cases whit normal karyotype.The patients with multilineage dysplasia(MLD)were more in MDS with trisomy 8,but the patients with excess blast(EB)were less(?~2=6.972,P<0.05).Bone marrow blasts in MDS with trisomy 8(mean rank=37.06)were lower than MDS with normal karyotype(mean rank=49.12)(U=622.5,Z=-2.036,P=0.042).Comparing the clinical and laboratory characteristics between U2AF1 mutated cases and U2AF1 wild-type cases in MDS with trisomy8,distributions of age,gender,WHO classifications,IPSS-R score and other laboratory indexes were not statistically significant different.Conclusions The patients in MDS with trisomy 8 have unique molecular characteristics.Close to90%of such patients harbor at least one gene mutation.U2AF1 is the most frequently mutated gene and has some correlations with+8 chromosomal abnormality,but do not significantly correlate with clinical and laboratory characteristics,such as neutropenia,anemia,thrombocytopenia and bone marrow excess blasts.