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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
Author(s) -
Díez Orland,
Osorio Ana,
Durán Mercedes,
MartinezFerrandis José Ignacio,
Hoya Miguel de la,
Salazar Raquel,
Vega Ana,
Campos Berta,
RodríguezLópez Raquel,
Velasco Eladio,
Chaves Javier,
DíazRubio Eduardo,
Jesús Cruz Juan,
Torres María,
Esteban Eva,
Cervantes Andrés,
Alonso Carmen,
San Román Juan Manuel,
GonzálezSarmiento Rogelio,
Miner Cristina,
Carracedo Angel,
Eugenia Armengod María,
Caldés Trinidad,
Benítez Javier,
Baiget Montserrat
Publication year - 2003
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.10260
Subject(s) - ovarian cancer , biology , breast cancer , genetics , cancer , founder effect , mutation , exon , brca2 protein , gene , germline mutation , oncology , genotype , medicine , haplotype
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 187underscore;188delAG, 330A>G, 5236G>A, 5242C>A, and 589underscore;590del (numbered after GenBank U14680) account for 46.6% of BRCA1 detected mutations whereas 3036underscore;3039del, 6857underscore;6858del, 9254underscore;9258del, and 9538underscore;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 6857underscore;6858del and 9254underscore;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. Hum Mutat 22:301–312, 2003. © 2003 Wiley‐Liss, Inc.