Moradian Mike M, Babikyan Davit T, Markarian Sione, Petrosyan Jonny G, Avanesian Nare, Arutunyan Tereza, Sarkisian Tamara F
Department of Medical Genetics, Yerevan State Medical University, Yerevan, Armenia.
Department of Molecular Genetics, Morava Scientific & Technology Services, Glendale, CA, USA.
Hum Genome Var. 2021 Feb 9;8(1):9. doi: 10.1038/s41439-021-00140-2.
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）可通过对致癌基因进行基因检测来识别。在本研究中，我们在76名有癌症家族史或40岁前患乳腺癌的亚美尼亚裔个体中鉴定出一系列基因变异。我们使用靶向遗传性综合癌症检测板（127个基因）对76名疑似HBOC患者及其家庭成员以及4名健康对照进行了筛查。我们在44名患者（58%）的6个基因中发现了26个致病性（path）和6个可能致病性（LPath）变异；这些变异存在于BRCA1（17个）、BRCA2（19个）、CHEK2（4个）、PALB2（2个）和NBN（1个）基因中。在不相关个体中发现了一些不同的变异；最值得注意的是，BRCA1基因中的p.Trp1815Ter变异出现在4名不相关患者中。我们在5名患者中未发现任何已知的显著变异。综合癌症检测板检测揭示了除BRCA1和BRCA2之外的癌症基因中的致病性变异，这表明仅检测BRCA1和BRCA2会使44名疑似HBOC患者中的8名（18%）漏检。这些数据还证实，综合癌症检测板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。
