RT info:eu-repo/semantics/article T1 Increased co-occurrence of pathogenic variants in hereditary breast and ovarian cancer and Lynch syndromes: A consequence of multigene panel genetic testing? A1 Infante Sanz, María Del Mar A1 Arranz Ledo, Mónica A1 Lastra, Enrique A1 Abella, Luis Enrique A1 Ferreira, Raquel A1 Orozco, Marta A1 Hernández, Lara A1 Martínez Martín, Noemí A1 Duran Dominguez, María Mercedes K1 Breast - Cancer K1 Ovaries - Cancer K1 Breast - Cancer - Genetic aspects K1 Ovaries - Cancer - Genetic aspects K1 Tumors - Genetic aspects K1 Cancer - Genetic aspects K1 Mamas - Cáncer K1 Ovarios - Cáncer K1 Genética molecular humana K1 2302.21 Biología Molecular K1 3201.02 Genética Clínica K1 3201.04 Patología Clínica AB The probability of carrying two pathogenic variants (PVs) in dominant cancer-predisposing genes for hereditary breast and ovarian cancer and lynch syndromes in the same patient is uncommon, except in populations where founder effects exist. Two breast cancer women that are double heterozygotes (DH) for both BRCA1/BRCA2, one ovarian cancer case DH for BRCA1/RAD51C, and another breast and colorectal cancer who is DH for BRCA2/PMS2 were identified in our cohort. Ages at diagnosis and severity of disease in BRCA1/BRCA2 DH resembled BRCA1 single-carrier features. Similarly, the co-existence of the BRCA2 and PMS2 mutations prompted the development of breast and colorectal cancer in the same patient. The first BRCA1/BRCA2 DH was identified by HA-based and Sanger sequencing (1 of 623 families with BRCA PVs). However, this ratio has increased up to 2.9% (1 DH carrier vs. 103 single PV carriers) since using a custom 35-cancer gene on-demand panel. The type of cancer developed in each DH patient was consistent with the independently inherited condition, and the clinical outcome was no worse than in patients with single BRCA1 mutations. Therefore, the clinical impact, especially in patients with two hereditary syndromes, lies in genetic counseling tailor-made for each family based on the clinical guidelines for each syndrome. The number of DH is expected to be increased in the future as a result of next generation sequencing routines. PB MDPI SN 1422-0067 YR 2022 FD 2022 LK https://uvadoc.uva.es/handle/10324/61502 UL https://uvadoc.uva.es/handle/10324/61502 LA eng NO International Journal of Molecular Sciences, 2022, Vol. 23, Nº. 19, 11499 NO Producción Científica DS UVaDOC RD 27-dic-2024