| Objective This study aims to investigate the clinical features and prognostic significance of MDS patients with BCOR/BCORL1 gene mutation and its co-mutation which mutation frequency is high.And the effect of co-mutation genes on prognosis of BCOR/BCORL1 mutation MDS patients is analyzed.Methods Next-generation sequencing was used to detect 34-myeloid-tumor-gene including BCOR and BCORL1 in 135 patients with de novo MDS who were diagnosed from September 2015 to September 2019.The clinical characteristics of BCOR/BCORL1 mutation in MDS patients were analyzed.MDS patients were classified according to WHO(2016)criteria,and 135 newly treated MDS patients were covered based on exclusion and diagnostic criteria.The main clinical characteristics of MDS patients with or without BCOR/BCORL1 mutation,co-mutation status,correlation between BCOR/BCORL1 mutation and co-mutation genes,influence of co-mutation genes on prognosis of MDS patients,influence of BCOR/BCORL1 mutation and whether the combination of other gene mutations on progression-free survival(PFS)and overall survival(OS)of MDS patients were analyzed.Results1.In MDS patients,the detection rate of BCOR/BCORL1 mutation was 25.2%(34patients).Of these,the mutation rate of BCOR was 11.9%(16 patients)and the mutation rate of BCORL1 was 13.3%(18 patients).There were no statistically significant differences in age,white blood cell,hemoglobin,platelet and bone marrow proportion between BCOR/BCORL1 mutation patients and non-mutation patients(P=0.899, P=0.053,P=0.141,P=0.784,P=0.322).Patients with BCOR/BCORL1 mutation were more common in women and lower neutrophil count than whom without BCOR/BCORL1 mutation [0.75(0.08-22.20)vs 1.27(0.06-35.71)×109/L,P=0.047].There were no significant difference in the rate of BCOR/BCORL1 mutation in different IPSS-R subgroups or between the IPSS-R lower risk group and the IPSS-R higher risk group(P=0.725,P=0.713).In different genetic groups and the conversion to leukemia group and the non-conversion to leukemia group,the mutation rate of BCOR/BCORL1 were also not significantly different(P=0.273,P=0.165).2.BCOR/BCORL1 gene was associated with DNMT3 A,NF1,STAG2,U2AF1,and EZH2 mutation(P=0.003,P=0.007,P<0.001,P=0.004,P=0.024).3.Compared with MDS patients without BCOR/BCORL1 mutation,the PFS of patients with BCOR/BCORL1 mutation were not significantly different(P=0.210),but the median OS was significantly shorter [16(3-32)vs 20(0.2-48)months,P=0.039].COX regression model analysis showed that BCOR/BCORL1 mutation was not an independent prognostic factor for OS in MDS patients(HR=1.305,95%CI 0.787-2.163,P=0.302).4.Survival analysis showed that U2AF1,EZH2,ZRSR,SRSF2,and SETBP1 mutations were all associated with shorter OS in MDS patients(P=0.041,P=0.025,P=0.016,P=0.017,P=0.002).The result of COX regression model analysis indicated that SRSF2 and SETBP1 mutations were independent adverse prognostic factors(HR=0.480,95%CI 0.261-0.884,P=0.018;HR=0.329,95%CI 0.109-0.992,P=0.048).5.In MDSpatients with BCOR/BCORL1 mutation,the survival analysis results showed that the median OS of patients with U2AF1 mutation,SRSF2 mutation and SETBP1 mutation was significantly shorter than that of those without the above gene mutations,with statistical significance(P=0.015,P=0.010,P<0.001).Conclusions1.BCOR/BCORL1 mutation was more common in MDS patients and often company with DNMT3 A,NF1,STAG2,U2AF1 and EZH2 mutation.2.BCOR/BCORL1 mutation was not associated with disease progression and AML transformation in MDS patients.3.Among co-mutantions with high frequency of BCOR/BCORL1 mutations,U2AF1,EZH2,ZRSR,SRSF2,and SETBP1 mutations were associated with poorer OS in MDS patients,and SRSF2 and SETBP1 mutations were independent prognostic factors in MDS patients.4.BCOR/BCORL1 mutation predicts poor survival in MDS patients,but is not an independent prognostic factor.It is considered to be related to the effect of co-mutated genes on prognosis. |
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