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

Autor(es):Mostrar menos -

Felicio, Paula S. ^[1] ; Grasel, Rebeca S. ^[1] ; Campacci, Natalia ^[1] ; de Paula, Andre E. ^[2] ; Galvao, Henrique C. R. ^[3] ; Torrezan, Giovana T. ^[4] ; Sabato, Cristina S. ^[2] ; Fernandes, Gabriela C. ^[2] ; Souza, Cristiano P. ^[3] ; Michelli, Rodrigo D. ^[3] ; Andrade, Carlos E. ^[3] ; De Figueiredo Barros, Bruna Duraes ^[4] ; Matsushita, Marcus M. ^[5] ; Revil, Timothee ^[6] ; Ragoussis, Jiannis ^{[6, 7]} ; Couch, Fergus J. ^{[8, 9]} ; Hart, Steven N. ^{[8, 9]} ; Reis, Rui M. ^{[10, 11, 1, 2]} ; Melendez, Matias E. ^{[1, 12, 13]} ; Tonin, Patricia N. ^{[6, 14, 15]} ; Carraro, Dirce M. ^{[4, 16]} ; Palmero, I, Edenir

Afiliação do(s) autor(es):Mostrar menos -

^[1] I, Barretos Canc Hosp, Mol Oncol Res Ctr, Rua Antenor Duarte Villela 1331, BR-14784400 Barretos, SP - Brazil

^[2] I, Barretos Canc Hosp, Ctr Mol Diag, Barretos, SP - Brazil

^[3] Barretos Canc Hosp, Dept Oncogenet, Barretos - Brazil

^[4] CIPE AC Camargo Canc Ctr, Genom & Mol Biol Grp, Sao Paulo - Brazil

^[5] Barretos Canc Hosp Barretos, Dept Pathol, Sao Paulo - Brazil

^[6] McGill Univ, Dept Human Genet, Montreal, PQ - Canada

^[7] McGill Univ, McGill Genome Ctr, Montreal, PQ - Canada

^[8] Mayo Clin, Dept Hlth Sci Res, Rochester, MN - USA

^[9] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN - USA

^[10] ICVS 3Bs PT Govt Associate Lab, Braga, Guimaraes - Portugal

^[11] Univ Minho, Med Sch, Life & Hlth Sci Res Inst ICVS, Braga - Portugal

^[12] I, Pele Little Prince Res Inst, Curitiba, Parana - Brazil

^[13] I, Fac Pequeno Principe, Curitiba, Parana - Brazil

^[14] McGill Univ, Dept Med, Montreal, PQ - Canada

^[15] McGill Univ, Hlth Ctr, Res Inst, Canc Res Program, Montreal, PQ - Canada

^[16] AC Camargo Canc Ctr, Genom Diagnost Ctr, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Human mutation; v. 42, n. 3 DEC 2020.
• Citações Web of Science: 1

Resumo

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. (AU)

• Processo FAPESP: 13/24633-2 - Caracterização molecular de famílias de alto risco para câncer de mama hereditário, negativas para mutações nos genes BRCA1/BRCA2: à procura do BRCAx
• Beneficiário: Edenir Inêz Palmero
• Modalidade de apoio: Auxílio à Pesquisa - Regular