BRCA1 testing in breast and/or ovarian cancer families from northeastern France identifies two common mutations with a founder effect.

The purpose of this study was to determine whether two mutations detected frequently in a population of breast and/or ovarian cancer families originating from the northeastern part of France could be due to a founder effect.,83 index cases of families ascertained to have a familial breast and/or ovarian cancer history, were screened for mutations in all coding exons of the BRCA1 gene, using combined DGGE and direct sequencing. For haplotype analysis, six polymorphic markers were used for allelotyping of mutation carriers and non carriers from nine families with 3600del11 mutation and four families with G1710X mutation.,Of 83 index cases, 27 (32%) had 14 different BRCA1 mutations, one of which (G1710X), had not been reported in other populations. Two mutations were particularly common: 3600del11 in exon 11 accounted for 37% and the nonsense mutation G1710X in exon 18 for 15% of all mutations. We identified a common haplotype for each mutation suggesting a common founder for each recurrent mutation. No specific phenotype could be assigned to any of the common mutations.,These data demonstrate geographical clustering and suggest a founder effect for particular BRCA1 mutations, which identification will facilitate carrier detection in French families with breast cancer and breast and/or ovarian cancer.