靶向高通量测序检测卵巢癌患者易感基因突变与临床特征的相关性研究

Targeted High-Throughput Sequencing to Detect the Correlation between Susceptible Gene Mutations and Clinical Features in Patients with Ovarian Cancer

目的探讨卵巢癌易感基因突变与临床特征的关系。方法采用靶向高通量测序技术对35例卵巢癌患者的外周血进行BRCA1,BRCA2,CHEK2,PALB2,BRIP1,TP53,PTEN,STK11,CDH1,ATM,BARD1,MLH1,MRE11A,MSH2,MSH6,MUTYH,NBN,PMS1,PMS2,RAD50和RAD51C共21种易感基因进行测序,结合临床资料分析基因突变与卵巢癌的相关性。结果卵巢癌患者多以高级别浆液性卵巢癌晚期为主。35例卵巢癌患者中共检出已知致病突变19例,突变率54.3%,其中BRCA1基因突变7例(20.0%),BRCA2基因突变4例(11.4%),RAD51C基因突变2例(5.7%),CHEK2,ATM,RAD50,MSH2,MRE11A和TP53基因突变各1例。BRCA1/2基因突变和高级别浆液性卵巢癌相关(P=0.034),和家族史显著相关(P=0.003),与年龄、FIGO分期无显著相关性(P>0.05)。另外,发现两种新的基因突变,包括BRCA1基因c.438delC和RAD51C基因c.390_391delAA。结论BRCA1和BRCA2是卵巢癌最主要的胚系突变基因,该基因突变与遗传性卵巢癌显著相关。高通量基因测序技术可有效检测卵巢癌胚系易感基因的突变情况,为卵巢癌的早期诊断和预防提供科学依据。

Objective To investigate the relationship between ovarian cancer susceptibility gene mutations and clinical features.Methods Using target high-throughput sequencing technology to perform BRCA1,BRCA2,CHEK2,PALB2,BRIP1,TP53,PTEN,STK11,CDH1,ATM,BARD1,MLH1,MRE11A,MSH2,MSH6,MUTYH,NBN,PMS1,PMS2,RAD50 and RAD51C,a total of 21 susceptible gene were sequenced in 35 patients with ovarian cancer,and the correlation between gene mutations and ovarian cancer was analyzed based on clinical data.Results The patients with ovarian cancer were mostly high-grade serous ovarian cancer at the advanced stage.A total of 19 cases of known pathogenic mutations were detected in 35 cases of ovarian cancer,with a mutation rate of 54.3%,including 7 cases of BRCA1 gene mutation(20.0%),4 cases of BRCA2 gene mutation(11.4%),and 2 cases of RAD51C gene mutation(5.7%),CHEK2,ATM,RAD50,MSH2,MRE11A and TP53 gene mutations in 1 case each.BRCA1/2 gene mutation was correlated with high-grade serous ovarian cancer(P=0.034),and significantly correlated with family history(P=0.003),but not significantly correlated with age and FIGO staging(P>0.05).Furthermore,two new gene mutations have been discovered,including the BRCA1 gene c.438delC and the RAD51C gene c.390_391delAA.Conclusion BRCA1 and BRCA2 are the most important germline mutant genes in ovarian cancer,and significantly related to hereditary ovarian cancer.High-throughput gene sequencing technology can effectively detect the mutations of ovarian cancer susceptible genes and provide scientific basis for early diagnosis and prevention of ovarian cancer.