Hereditary breast and ovarian cancer (HBOC) can be identified by genetic testing of cancer-causing genes. In this study, we identified a spectrum of genetic variations among 76 individuals of Armenian descent either with a family history of cancer or breast cancer before the age of 40. We screened 76 suspected HBOC patients and family members as well as four healthy controls using a targeted and hereditary comprehensive cancer panel (127 genes). We found 26 pathogenic (path) and 6 likely pathogenic (LPath)variants in 6 genes in 44 patients (58%); these variants were found in BRCA1 (17), BRCA2 (19), CHEK2 (4), PALB2 (2), and NBN (1). A few different variants were found in unrelated individuals; most notably, variant p.Trp1815Ter in the BRCA1 gene occurred in four unrelated patients. We did not find any known significant variants in five patients. Comprehensive cancer panel testing revealed pathogenic variants in cancer genes other than BRCA1 and BRCA2, suggesting that testing only BRCA1 and BRCA2 would have missed 8 out of 44 suspected HBOC patients (18%). These data also confirm that a comprehensive cancer panel testing approach could be an appropriate way to identify most of the variants associated with hereditary breast cancer.

遗传性乳腺癌和卵巢癌 (HBOC) 可以通过致癌基因的基因检测来识别。在这项研究中，我们确定了 76 名 40 岁之前有癌症或乳腺癌家族史的亚美尼亚人后裔中的一系列遗传变异。我们筛选了 76 名疑似 HBOC 患者和家庭成员以及 4 名健康对照，使用靶向和遗传性综合癌症小组（127 个基因）。我们在 44 名患者 (58%) 的 6 个基因中发现了 26 个致病 (path) 和 6 个可能致病 (LPath) 变异；这些变异存在于BRCA1 (17)、BRCA2 (19)、CHEK2 (4)、PALB2 (2) 和NBN(1)。在不相关的个​​体中发现了一些不同的变体；最值得注意的是， BRCA1基因中的变体 p.Trp1815Ter发生在四名无关患者身上。我们在五名患者中没有发现任何已知的显着变异。综合癌症小组检测揭示了除BRCA1和BRCA2以外的癌症基因的致病变异，这表明仅检测BRCA1和BRCA2会漏掉 44 名疑似 HBOC 患者中的 8 名（18%）。这些数据还证实，全面的癌症小组检测方法可能是识别与遗传性乳腺癌相关的大多数变异的合适方法。