一例男性乳腺癌的罕见BRCA2基因胚系变异分析  

Identification of a novel germline BRCA2 variant in a male with breast cancer

作　　者：张峰 吴轲 Zhang Feng;Wu Ke(Department of Pathology,the Fourth Affiliated Hospital of Zhejiang University School of Medicine,Yiwu,Zhejiang 322000,China)

机构地区：[1]浙江大学医学院附属第四医院病理科,义乌322000 [2]义乌市妇幼保健院产前诊断中心,义乌322000

出　　处：《中华医学遗传学杂志》2022年第3期330-333,共4页Chinese Journal of Medical Genetics

基　　金：2018年义乌市科研计划项目(18-3-104)。

摘　　要：目的对1例男性乳腺癌患者的基因组变异进行分析,为检测后的遗传咨询提供依据。方法检测前了解家族史、医疗史,告知被检者检测潜在的风险及可能的检测结果,利用二代测序技术对先证者进行全外显子组检测,应用Sanger测序对先证者及家系成员进行变异位点验证。结果二代测序结果显示先证者BRCA2基因存在c.6018dupT(p.Thr2007Tyr*11)杂合变异,是未报道过的新变异,属于移码变异。该变异会导致BRCA2基因mRNA的翻译提前终止,产生截短的BRCA2蛋白,根据美国医学遗传学与基因组学学会遗传变异分类标准与指南,BRCA2基因c.6018dupT变异判定为致病(PVS1+PM1/2+PP4)。结论BRCA2基因c.6018dupT变异可能是该家系男性乳腺癌患者的遗传学病因,新变异位点的检出丰富了BRCA2基因变异谱。Objective To explore the genetic basis for a male with breast cancer and a sister who had deceased of the disease.Methods Medical and family history of the proband was collected.Next-generation sequencing was carried out to detect potential variant associated with breast cancer,and Sanger sequencing was used to verify the result.Results The proband was found to harbor a novel heterozygous c.6018dupT variant of the BRCA2 gene which may cause premature termination of mRNA translation,resulting in a truncated protein.Combined with the family history,the variant was deduced to be a germline mutation.Based on the American College of Medical Genetics and Genomics standards and guidelines,c.6018dupT variant of BRCA2 gene was predicted to be pathogenic(PVS1+PM1/2+PP4).Conclusion The germline variant of the BRCA2 gene probably underlay the breast cancer in this pedigree.

关 键 词：男性乳腺癌 BRCA2基因 二代测序技术 

分 类 号：R737.9[医药卫生—肿瘤]