Whole-exome sequencing of non-BRCA1/BRCA2 mutation carrier cases at high-risk for hereditary breast/ovarian cancer.

Autor: Felicio PS; Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil., Grasel RS; Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil., Campacci N; Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil., de Paula AE; Center of Molecular Diagnosis, Barretos Cancer Hospital, Barretos, São Paulo, Brazil., Galvão HCR; Department of Oncogenetics, Barretos Cancer Hospital, Barretos, Brazil., Torrezan GT; Genomics and Molecular Biology Group, CIPE - A. C. Camargo Cancer Center, São Paulo, Brazil., Sabato CS; Center of Molecular Diagnosis, Barretos Cancer Hospital, Barretos, São Paulo, Brazil., Fernandes GC; Center of Molecular Diagnosis, Barretos Cancer Hospital, Barretos, São Paulo, Brazil., Souza CP; Department of Oncogenetics, Barretos Cancer Hospital, Barretos, Brazil., Michelli RD; Department of Oncogenetics, Barretos Cancer Hospital, Barretos, Brazil., Andrade CE; Department of Oncogenetics, Barretos Cancer Hospital, Barretos, Brazil., Barros BDF; Genomics and Molecular Biology Group, CIPE - A. C. Camargo Cancer Center, São Paulo, Brazil., Matsushita MM; Department of Pathology, Barretos Cancer Hospital Barretos, Sao Paulo, Brazil., Revil T; Department of Human Genetics, McGill University, Montreal, Canada., Ragoussis J; Department of Human Genetics, McGill University, Montreal, Canada.; McGill Genome Centre, University of McGill, Montreal, Canada., Couch FJ; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.; Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota., Hart SN; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.; Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota., Reis RM; Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil.; Center of Molecular Diagnosis, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.; Life and Health Sciences Research Institute (ICVS), Medical School, University of Minho, Braga, Portugal.; ICVS/3B's-PT Government Associate Laboratory, Braga, Guimarães, Portugal., Melendez ME; Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil.; Pele Little Prince Research Institute, Curitiba, Brazil.; Faculdades Pequeno Príncipe, Curitiba, Brazil., Tonin PN; Department of Human Genetics, McGill University, Montreal, Canada.; Department of Medicine, McGill University, Montreal, Canada.; Cancer Research Program, The Research Institute of the McGill University Health Centre, Montreal, Canada., Carraro DM; Genomics and Molecular Biology Group, CIPE - A. C. Camargo Cancer Center, São Paulo, Brazil.; Genomic Diagnostic Center, AC Camargo Cancer Center, São Paulo, Brazil., Palmero EI; Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil.; Center of Molecular Diagnosis, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.; Pele Little Prince Research Institute, Curitiba, Brazil.; Faculdades Pequeno Príncipe, Curitiba, Brazil.
Jazyk: angličtina
Zdroj: Human mutation [Hum Mutat] 2021 Mar; Vol. 42 (3), pp. 290-299. Date of Electronic Publication: 2020 Dec 28.
DOI: 10.1002/humu.24158
Abstrakt: 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.
(© 2020 The Authors. Human Mutation published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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