Sukumar Jasmine, Kassem Mahmoud, Agnese Doreen, Pilarski Robert, Ramaswamy Bhuvaneswari, Sweet Kevin, Sardesai Sagar
Division of Medical Oncology, The Ohio State University Wexner Medical Center, 1204A Lincoln Tower, 1800 Cannon Dr., Columbus, OH, 43210, USA.
Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
Breast Cancer Res Treat. 2021 Apr;186(2):569-575. doi: 10.1007/s10549-021-06095-w. Epub 2021 Jan 28.
Concurrent germline (g) pathogenic variants related to hereditary breast cancer represent a rare occurrence. While double heterozygosity in gBRCA1 and gBRCA2 has been reported in the past, herein we describe the first case of three known concurrent pathogenic variants identified in a family with a strong history of breast cancer. Case presentation The proband is a 55-year-old female diagnosed with synchronous bilateral breast cancers. She underwent a multi-gene panel testing indicating the presence of 3 concurrent heterozygous germline deleterious variants in BRCA1 (c.181T > G), BRCA2 (c.4398_4402delACATT), and CHEK2 (1100delC). The patient's two daughters (34 and 29 years-old) were found to be transheterozygous for inherited pathogenic variants in BRCA1 (c.181T > G) and CHEK2 (1100delC) genes.
The cancer risk and phenotypic manifestations associated with transheterozygous or multiple concurrent deleterious germline variants in hereditary breast cancer requires further investigation. A personalized approach to counseling, screening, and risk reduction should be undertaken for these individuals.
与遗传性乳腺癌相关的同时存在的种系（g）致病变异很少见。虽然过去曾报道过gBRCA1和gBRCA2的双重杂合性，但在此我们描述了在一个有强烈乳腺癌家族史的家庭中首次发现的三例已知同时存在的致病变异病例。病例报告 先证者是一名55岁女性，被诊断为同步双侧乳腺癌。她接受了多基因panel检测，结果显示在BRCA1（c.181T＞G）、BRCA2（c.4398_4402delACATT）和CHEK2（1100delC）中同时存在3个杂合种系有害变异。患者的两个女儿（34岁和29岁）被发现为BRCA1（c.181T＞G）和CHEK2（1100delC）基因中遗传性致病变异的反式杂合子。
遗传性乳腺癌中与反式杂合或多个同时存在的有害种系变异相关的癌症风险和表型表现需要进一步研究。应对这些个体采取个性化的咨询、筛查和降低风险方法。
