title: Screening for large rearrangements of the BRCA2 gene in Spanish families with breast/ovarian cancer.
abstract: Germ-line mutations in BRCA1 and BRCA2 are responsible for about 30-60% of the hereditary breast and ovarian cancer (HBOC). A large number of point mutations have been described in both genes. However, large deletions and duplications that disrupt one or more exons are overlooked by point mutation detection approaches. Over the past years several rearrangements have been identified in BRCA1, while few studies have been designed to screen this type of mutations in BRCA2. Our aim was to estimate the prevalence of large genomic rearrangements in the BRCA2 gene in Spanish breast/ovarian cancer families. The multiplex ligation-dependent probe amplification (MLPA) was employed to search gross deletions or duplications of BRCA2 in 335 Spanish moderate to high-risk breast/ovarian cancer families previously screened negative for point mutations by conventional methods. Four different and novel large genomic alterations were consistently identified by MLPA in five families, respectively: deletions of exon 2, exons 10-12 and exons 15-16 and duplication of exon 20 (in two families). RT-PCR experiments confirmed the deletion of exons 15-16. All patients harbouring a genomic rearrangement were members of high-risk families, with three or more breast/ovarian cancer cases or the presence of breast cancer in males. We provide evidence that the BRCA2 rearrangements seem to account for a relatively small proportion of familial breast cancer cases in Spanish population. The screening for these alterations as part of the comprehensive genetic testing can be recommended, especially in multiple case breast/ovarian families and families with male breast cancer cases.
authors.affiliation: Servei de Genètica, Hospital de la Santa Creu i Sant Pau, Pare Claret 167, Barcelona 08025, Spain. Sgutierrez@santpau.es
authors.forename: Sara
authors.initials: S
authors.lastname: Gutiérrez-Enríquez
authors.forename: Miguel
authors.initials: M
authors.lastname: de la Hoya
authors.forename: Cristina
authors.initials: C
authors.lastname: Martínez-Bouzas
authors.forename: Ana
authors.initials: A
authors.lastname: Sanchez de Abajo
authors.forename: Teresa
authors.initials: T
authors.lastname: Ramón y Cajal
authors.forename: Gemma
authors.initials: G
authors.lastname: Llort
authors.forename: Ignacio
authors.initials: I
authors.lastname: Blanco
authors.forename: Elena
authors.initials: E
authors.lastname: Beristain
authors.forename: Eduardo
authors.initials: E
authors.lastname: Díaz-Rubio
authors.forename: Carmen
authors.initials: C
authors.lastname: Alonso
authors.forename: María-Isabel
authors.initials: MI
authors.lastname: Tejada
authors.forename: Trinidad
authors.initials: T
authors.lastname: Caldés
authors.forename: Orland
authors.initials: O
authors.lastname: Diez
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D018567:Breast Neoplasms, Male / Q000453:epidemiology / Q000235:genetics; D002872:Chromosome Deletion; D005192:Family Health; D005260:Female; D020440:Gene Duplication; D024522:Genes, BRCA2; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010051:Ovarian Neoplasms / Q000453:epidemiology / Q000235:genetics*; D013030:Spain / Q000453:epidemiology