RT info:eu-repo/semantics/article
T1 About 1% of the breast and ovarian Spanish families testing negative for BRCA1 and BRCA2 are carriers of RAD51D pathogenic variants
A1 Gutiérrez-Enríquez, Sara
A1 Esteban Cardeñosa, Eva
A1 Díaz Rubio, Eduardo
A1 Hoya, Miguel de la
A1 Gutiérrez Enríquez, Sara
A1 Bonache, Sandra
A1 Ruíz de Garibay, Gorka
A1 Osorio, Ana
A1 Santamariña, Marta
A1 Ramón y Cajal, Teresa
A1 Esteban Cardeñosa, Eva
A1 Tenés, Anna
A1 Yanowsky, Kira
A1 Barroso, Alicia
A1 Montalban, Gemma
A1 Blanco, Eva
A1 Cornet, Mònica
A1 Gadea, Neus
A1 Infante Sanz, María del Mar
A1 Caldés, Trinidad
A1 Díaz Rubio, Eduardo
A1 Balmaña, Judith
A1 Lasa, Adriana
A1 Vega, Ana
A1 Benítez, Javier
A1 Hoya, Miguel de la
A1 Diez, Orland
K1 RAD51D
K1 Cáncer
K1 Predisposición genética
K1 Cáncer-Prevención
K1 24 Ciencias de la Vida
AB RAD51D mutations have been recently identified in breast (BC) and ovarian cancer (OC) families. Although an etiological role in OC appears to be present, the association of RAD51D mutations and BC risk is more unclear. We aimed to determine the prevalence of germline RAD51D mutations in Spanish BC/OC families negative for BRCA1/BRCA2 mutations. We analyzed 842 index patients: 491 from BC/OC families, 171 BC families, 51 OC families and 129 patients without family history but with early-onset BC or OC or metachronous BC and OC. Mutation detection was performed with high-resolution melting, denaturing high-performance liquid chromatography or Sanger sequencing. Three mutations were found in four families with BC and OC cases (0.82%). Two were novel: c.1A>T (p.Met1?) and c.667+2_667+23del, leading to the exon 7 skipping and one previously described: c.674C>T (p.Arg232*). All were present in BC/OC families with only one OC. The c.667+2_667+23del cosegregated in the family with one early-onset BC and two bilateral BC cases. We also identified the c.629C>T (p.Ala210Val) variant, which was predicted in silico to be potentially pathogenic. About 1% of the BC and OC Spanish families negative for BRCA1/BRCA2 are carriers of RAD51D mutations. The presence of several BC mutation carriers, albeit in the context of familial OC, suggests an increased risk for BC, which should be taken into account in the follow-up and early detection measures. RAD51D testing should be considered in clinical setting for families with BC and OC, irrespective of the number of OC cases in the family.
PB Wiley
SN 0020-7136
YR 2014
FD 2014
LK https://uvadoc.uva.es/handle/10324/47405
UL https://uvadoc.uva.es/handle/10324/47405
LA eng
NO International Journal of Cancer, 2014, vol. 134, n. 9, p. 2088
NO Producción Científica
DS UVaDOC
RD 27-nov-2024