BRCA1 and BRCA2 in breast cancer families from Wales: moderate mutation frequency and two recurrent mutations in BRCA1.

Jm Lancaster,J Gray,C Gumbs,Pa Futreal,E France,R Wiseman,D Wheeler,P Harper,J Sampson,Me Carney,J Myring

doi:10.1038/bjc.1998.701

Abstract

Mutations in the BRCA1/BRCA2 genes account for varying proportions of breast cancer families studied, and demonstrate considerable variation in mutational spectra coincident with ethnic and geographical diversity. We have screened for mutations in 17 families from Wales with two or more cases of breast cancer under age 50 and/or ovarian cancer. Eight out of 17 (47%) families had demonstrable mutations. Six out of 17 (35%) carried BRCA1 mutations and 2 out of 17 (12%) carried BRCA2 mutations. Two recurrent mutations in BRCA1 were identified, which appear to represent founder mutations in this population. These data support the existence of additional breast and ovarian cancer susceptibility genes.

Highlights

Inactivating mutations were identified in 8 out of 17 (47%) families - six in BRCAJ (35%) and two in BRCA2 (12%) (Table 1)
No BRCA2 mutations were observed in breast/ovarian families
17 Welsh families with apparent hereditary breast/ovarian cancer were studied for BRCAI/BRCA2 mutations

Summary

Introduction

BRCAJ and BRCA2, have been identified as being causative in familial breast/ovarian cancer (Miki et al, 1994; Wooster et al, 1995). Carriers of germline mutations in these genes are at increased risk of developing breast and ovarian cancers. We have screened affected individuals from 17 high-risk Welsh breast and breast/ovarian cancer families for mutations in both BRCAJ and BRCA2 to determine the proportion of families attributable to defects in these genes.

Results

Conclusion