title: Analysis of BRCA1 and BRCA2 genes in Spanish breast/ovarian cancer patients: a high proportion of mutations unique to Spain and evidence of founder effects.
abstract: We screened index cases from 410 Spanish breast/ovarian cancer families and 214 patients (19 of them males) with breast cancer for germ-line mutations in the BRCA1 and BRCA2 genes, using SSCP, PTT, CSGE, DGGE, and direct sequencing. We identified 60 mutations in BRCA1 and 53 in BRCA2. Of the 53 distinct mutations observed, 11 are novel and 12 have been reported only in Spanish families (41.5%). The prevalence of mutations in this set of families was 26.3%, but the percentage was higher in the families with breast and ovarian cancer (52.1%). The lowest proportion of mutations was found in the site-specific female breast cancer families (15.4%). Of the families with male breast cancer cases, 59.1% presented mutations in the BRCA2 gene. We found a higher frequency of ovarian cancer associated with mutations localized in the 5' end of the BRCA1 gene, but there was no association between the prevalence of this type of cancer and mutations situated in the ovarian cancer cluster region (OCCR) region of exon 11 of the BRCA2 gene. The mutations 187_188delAG, 330A>G, 5236G>A, 5242C>A, and 589_590del (numbered after GenBank U14680) account for 46.6% of BRCA1 detected mutations whereas 3036_3039del, 6857_6858del, 9254_9258del, and 9538_9539del (numbered after GenBank U43746) account for 56.6% of the BRCA2 mutations. The BRCA1 330A>G has a Galician origin (northwest Spain), and BRCA2 6857_6858del and 9254_9258del probably originated in Catalonia (northeast Spain). Knowledge of the spectrum of mutations and their geographical distribution in Spain will allow a more effective detection strategy in countries with large Spanish populations.
authors.affiliation: Servei de Genètica, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. Odiez@hsp.santpau.es
authors.forename: Orland
authors.initials: O
authors.lastname: Díez
authors.forename: Ana
authors.initials: A
authors.lastname: Osorio
authors.forename: Mercedes
authors.initials: M
authors.lastname: Durán
authors.forename: José Ignacio
authors.initials: JI
authors.lastname: Martinez-Ferrandis
authors.forename: Miguel
authors.initials: M
authors.lastname: de la Hoya
authors.forename: Raquel
authors.initials: R
authors.lastname: Salazar
authors.forename: Ana
authors.initials: A
authors.lastname: Vega
authors.forename: Berta
authors.initials: B
authors.lastname: Campos
authors.forename: Raquel
authors.initials: R
authors.lastname: Rodríguez-López
authors.forename: Eladio
authors.initials: E
authors.lastname: Velasco
authors.forename: Javier
authors.initials: J
authors.lastname: Chaves
authors.forename: Eduardo
authors.initials: E
authors.lastname: Díaz-Rubio
authors.forename: Juan
authors.initials: J
authors.lastname: Jesús Cruz
authors.forename: María
authors.initials: M
authors.lastname: Torres
authors.forename: Eva
authors.initials: E
authors.lastname: Esteban
authors.forename: Andrés
authors.initials: A
authors.lastname: Cervantes
authors.forename: Carmen
authors.initials: C
authors.lastname: Alonso
authors.forename: Juan Manuel
authors.initials: JM
authors.lastname: San Román
authors.forename: Rogelio
authors.initials: R
authors.lastname: González-Sarmiento
authors.forename: Cristina
authors.initials: C
authors.lastname: Miner
authors.forename: Angel
authors.initials: A
authors.lastname: Carracedo
authors.forename: María
authors.initials: M
authors.lastname: Eugenia Armengod
authors.forename: Trinidad
authors.initials: T
authors.lastname: Caldés
authors.forename: Javier
authors.initials: J
authors.lastname: Benítez
authors.forename: Montserrat
authors.initials: M
authors.lastname: Baiget
mesh_terms: D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics*; D018567:Breast Neoplasms, Male / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D018703:Founder Effect; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics*; D011110:Polymorphism, Genetic; D013030:Spain