遗传性卵巢癌中乳腺癌抑制蛋白1/2和错配修复蛋白MutS同源物2基因突变的意义研究

Analysis of breast cancer suppressor protein 1/2 and mismatch repair protein MutS homolog 2 gene mutations in hereditary ovarian cancer

目的研究遗传性卵巢癌中乳腺癌抑制蛋白1/2(BRCA1/2)和错配修复蛋白MutS同源物2(MSH2)基因突变意义。方法选取2019年6月至2023年6月于新余市人民医院就诊的13例家族遗传性卵巢癌患者及家系中5名Ⅰ代健康亲属、20名Ⅱ/Ⅲ代健康亲属作为研究对象。采集所有研究对象空腹静脉血5 ml,分离提取DNA行聚合酶链式反应扩增后直接测序比对,研究遗传性卵巢癌家族中有意义的错义突变基因。结果13例家族遗传性卵巢癌患者临床分期以Ⅲ期、组织分级以低-中分化、有淋巴结肿转移为主。13例患者基因测序显示,BRCA1基因发现突变6处中,无意义突变3处,新发现突变3处。新发现3处突变中3780A>G、5069A>G造成氨基酸变化,3326A>T突变造成Arg突变成终止密码子,共同存在突变为3326A>T。BRCA2基因测序检测出突变6处,无意义突变5处,其中共同存在突变为1342A>C。MSH2基因测序发现无意义突变2处。健康家系中,携带BRCA1基因3326A>T突变3例(12.00%),携带BRCA2基因1342A>C突变12例(48.00%),其余女性测序结果正常。结论BRCA1基因杂合突变3326A>T和BRCA2基因杂合突变1342A>C是遗传性卵巢癌家族发病的致病基因,可为临床早发现、早诊断、早治疗提供指导。

Objective To study the significance of breast cancer suppressor protein 1/2(BRCA1/2)and mismatch repair protein MutS homolog 2(MSH2)gene mutations in hereditary ovarian cancer.Methods 13 patients with familial hereditary ovarian cancer who visited Xinyu People's Hospital from June 2019 to June 2021,5 healthy relatives in generationⅠand 20 healthy relatives in generationⅡ/Ⅲwere selected as the study subjects.Collect 5 ml of fasting venous blood from all research subjects,isolate and extract DNA,perform polymerase chain reaction amplification,and directly sequence and compare it to study meaningful missense mutation genes in hereditary ovarian cancer families.Results 13 patients with familial hereditary ovarian cancer were clinically classified as stageⅢ,with low to medium differentiation and lymph node metastasis as the main histological grading.Gene sequencing of 13 patients showed 7 mutations were found in BRCA1 gene,and 3 were nonsignificant mutations,3 were new mutations.Among 3 new mutations,with 3780A>G and 5069A>G causing amino acid changes,and 3326A>T mutation causing Arg to mutate into a termination codon,the common mutation was 3326A>T.BRCA2 gene sequencing detected 6 mutations,and 5 were nonsignificant mutations,the common mutation was 1342A>C.MSH2 gene sequencing revealed 2 nonsignificant mutations.In the healthy family,there were 3(12.00%)cases with BRCA1 gene 3326A>T mutation,and there were 12(48.00%)cases with BRCA2 gene 1342A>C mutation,the sequencing results of other women were normal.Conclusion BRCA1 gene heterozygous mutation 3326A>T and BRCA2 gene heterozygous mutation 1342A>C are pathogenic genes in hereditary ovarian cancer families,providing guidance for early detection,diagnosis,and treatment in clinical practice.