1. Whole‐exome sequencing of non‐ BRCA1/BRCA2 mutation carrier cases at high‐risk for hereditary breast/ovarian cancer
- Author
-
Rui Manuel Reis, Henrique de Campos Reis Galvão, Rodrigo Augusto Depieri Michelli, Cristiano de Pádua Souza, Jiannis Ragoussis, Giovana Tardin Torrezan, Natalia Campacci, Timothée Revil, Fergus J. Couch, Patricia N. Tonin, Cristina da Silva Sabato, Bruna D. F. Barros, André Escremim de Paula, Rebeca Silveira Grasel, Carlos Eduardo Mattos da Cunha Andrade, Marcus Matsushita, Gabriela C Fernandes, Matias Eliseo Melendez, Paula Silva Felicio, Edenir Inêz Palmero, Steven N. Hart, and Dirce Maria Carraro
- Subjects
hereditary breast and ovarian cancer predisposition syndrome ,medicine.medical_specialty ,Genes, BRCA2 ,Population ,Loss of Heterozygosity ,Breast Neoplasms ,Biology ,Loss of heterozygosity ,03 medical and health sciences ,MUTYH ,Exome Sequencing ,Genetics ,PMS2 ,medicine ,Humans ,Genetic Predisposition to Disease ,education ,CHEK2 ,Research Articles ,Germ-Line Mutation ,Genetics (clinical) ,Exome sequencing ,030304 developmental biology ,BRCA2 Protein ,Ovarian Neoplasms ,0303 health sciences ,education.field_of_study ,BRCA1 Protein ,030305 genetics & heredity ,medicine.disease ,breast cancer predisposition ,hereditary cancer ,Mutation ,BRCAX ,Hereditary Breast and Ovarian Cancer Syndrome ,Medical genetics ,whole‐exome sequencing ,Female ,Ovarian cancer ,Research Article - Abstract
The current study aimed to identify new breast and/or ovarian cancer predisposition genes. For that, whole‐exome sequencing (WES) was performed in the germline DNA of 52 non‐BRCA1/BRCA2/TP53 mutation carrier women at high‐risk for hereditary breast and ovarian cancer (HBOC). All variants were classified using information from population and disease specific databases, in silico prediction tools and the American College of Medical Genetics and Genomics (ACMG) criteria. Loss of heterozygosity (LOH) of tumor samples and segregation analyses were performed whenever possible. The variants identified were investigated in a second, independent cohort of 17 BC cases. Pathogenic/Likely Pathogenic variants were identified in known cancer genes such as CHEK2, MUTYH, PMS2, and RAD51C. Rare and potentially pathogenic variants were identified in DNA repair genes (FAN1, POLQ, and RAD54L) and other cancer‐related genes such as DROSHA and SLC34A2. Interestingly, the variant c.149T>G in the FAN1 gene was identified in two unrelated families, and exhibited LOH in the tumor tissue of one of them. In conclusion, this is the largest Brazilian WES study involving families at high‐risk for HBOC which has brought novel insights into the role of potentially new genetic risk factors for hereditary breast and ovarian cancer., The current study aimed to identify new breast and/or ovarian cancer predisposition genes. Rare and potentially pathogenic variants were identified in DNA repair genes (FAN1, POLQ, and RAD54L) and other cancer‐related genes such as DROSHA and SLC34A2. This is the largest Brazilian WES study involving families at high‐risk for hereditary breast and ovarian cancer which has brought novel insights into the role of potentially new genetic risk factors for hereditary breast and ovarian cancer.
- Published
- 2020