RT info:eu-repo/semantics/article
T1 A PALB2 truncating mutation: Implication in cancer prevention and therapy of Hereditary Breast and Ovarian Cancer
A1 Velázquez, Carolina
A1 Esteban-Cardeñosa, Eva M.
A1 Lastra, Enrique
A1 Abella, Luis E.
A1 de la Cruz, Virginia
A1 Lobatón, Carmen D.
A1 Durán, Mercedes
A1 Infante, Mar
AB Explaining genetic predisposition in Hereditary Breast and Ovarian Cancer (HBOC) families without BRCA mutations is crucial. Germline PALB2 inactivating mutations were associated with an increased risk of HBOC due to its role in DNA repair through cooperation with BRCA proteins. The prevalence and penetrance of PALB2 mutations in Spanish HBOC patients remains unexplained. PALB2 mutation screening has been conducted in 160 high-risk BRCA-negative patients and 320 controls. We evaluated four predicted splicing disruption variants and large genomic rearrangements by multiplex ligation-dependent probe amplification. We have found a frameshift mutation which segregates in an early onset cancer family; and four rare missense variants. None of the variants tested for a predicted splicing disruption showed an aberrant transcript pattern. No large genomic rearrangements were detected. Although PALB2 truncating mutations are rarely identified, segregation analysis and early onset cancer suggest a significant contribution to HBOC susceptibility in the Spanish population. PALB2 screening may improve genetic counselling through prevention measures, pedigree management and PARP inhibitor therapy selection.
PB Elsevier
SN 0960-9776
YR 2019
FD 2019
LK https://uvadoc.uva.es/handle/10324/73283
UL https://uvadoc.uva.es/handle/10324/73283
LA spa
NO Breast. 2019 Feb,43:91-96
DS UVaDOC
RD 31-ene-2025