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 Durán Domínguez, 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 24-nov-2024