Abstract
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.
Highlights
Hereditary breast and ovarian cancer (HBOC) and their causative variants have become one of the most studied hereditary cancers
Variant p.Ile1159Metfs in BRCA1 was identified in the same family members from two different families, and p.Leu1669Ter in BRCA2 was identified in two sisters and one unrelated individual
These variants were found in known cancer-causing genes, such as ATR, BRCA1, CHEK2, MLH1, and MUTYH, and in two less prominent genes, SLX4 and WRAP53
Summary
Hereditary breast and ovarian cancer (HBOC) and their causative variants have become one of the most studied hereditary cancers. The BRCA1 (NM_007294.3) and BRCA2 (NM_000059.3) gene variants were the primary focus of such studies in the past, hereditary cancer panel testing has recently replaced the approach involving only the BRCA1 and BRCA2 genes. It has been shown that close to 10% of hereditary breast cancer can be caused by variants in genes such as CHEK2 (NM_007194.3), PALB2 (NM_024675.3), ATM (NM_000051.3), and MUTYH (NM_001128425.1)[1]. There are hundreds of genes that could be involved in tumorigenesis and cancer, yet not all there are several cancer-causing variants that could be more prevalent in an ethnic or specific population. The number of Official journal of the Japan Society of Human Genetics
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