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

Mike M Moradian; Davit T Babikyan; Sione Markarian; Jonny G Petrosyan; Nare Avanesian; Tereza Arutunyan; Tamara F Sarkisian

doi:10.1038/s41439-021-00140-2

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

Hum Genome Var. 2021 Feb 9;8(1):9. doi: 10.1038/s41439-021-00140-2.

Authors

Mike M Moradian^#^{1

2}, Davit T Babikyan^#^{3

4}, Sione Markarian⁵, Jonny G Petrosyan⁴, Nare Avanesian⁵, Tereza Arutunyan⁵, Tamara F Sarkisian^{3

4}

Affiliations

¹ Department of Medical Genetics, Yerevan State Medical University, Yerevan, Armenia. Moradian@Makgene.com.
² Department of Molecular Genetics, Morava Scientific & Technology Services, Glendale, CA, USA. Moradian@Makgene.com.
³ Department of Medical Genetics, Yerevan State Medical University, Yerevan, Armenia.
⁴ Department of Molecular Genetics, Center of Medical Genetics and Primary Health Care, Yerevan, Armenia.
⁵ Department of Molecular Genetics, Morava Scientific & Technology Services, Glendale, CA, USA.

^# Contributed equally.

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.