Germline mutational spectrum in Armenian breast cancer patients suspected of hereditary breast and ovarian cancer

• Published in: Human genome variation Vol. 8; no. 1; p. 9
• Main Authors: Moradian, Mike M., Babikyan, Davit T., Markarian, Sione, Petrosyan, Jonny G., Avanesian, Nare, Arutunyan, Tereza, Sarkisian, Tamara F.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 09.02.2021; Springer Nature B.V; Nature Publishing Group
• Subjects: 631/208/68; 692/420/2489/68; Biomedical and Life Sciences; Biomedicine; BRCA1 protein; BRCA2 protein; Breast cancer; Gene Expression; Gene Function; Gene Therapy; Genes; Genetic diversity; Genetic screening; Heredity; Human Genetics; Molecular Medicine; Ovarian cancer; Patients
• ISSN: 2054-345X; 2054-345X
• 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. Breast cancer: The spectrum of mutations in Armenian patients Genetic variants associated with hereditary breast cancer have been identified by a comprehensive analysis of Armenian patients, highlighting the need for testing panels to be tailored to the population being screened. A team led by Mike Moradian and Davit Babikyan of Yerevan State University Medical School, screened samples from 76 breast cancer patients of Armenian descent. Using a panel including 127 genes, they identified 32 pathogenic variants in 44 patients, mostly in BRCA1 or BRCA2 . However, testing only BRCA1 and BRCA2 would have missed 8 of these 44 patients. The analysis also found variants of unknown significance in 32 patients which might be involved in hereditary breast cancer. Based on this analysis, the researchers argue that it is important to screen with comprehensive gene panels to increase the chance of detecting variants associated with cancer.