Prevalence of BRCA1 and BRCA2 mutations among clinic-based African American families with breast cancer

To define the prevalence and relative contributions of BRCA1 and BRCA2 muta tions among African American families with boast cancer, we analyzed 28 DNA samples from patients identified through two oncology clinics. The entire coding regions of BRCA1 and BRCA2 were screened by protein truncation test, heteroduplex analysis, or single-stranded conformation polymorphism follow ed by DNA sequencing of variant bands. Deleterious protein-truncating BRCA1 and BRCA2 mutations were identified in five patients or 18% of the entire cohort. Only 8% (1 of 13) of women with a family history of breast cancer, but no ovarian cancer, had mutations. The mutation rates were higher for wo men from families with a history of breast cancer and at least one ovarian cancer (three of six, 50%). One woman with a family history of undocumented cancers was also found to carry a deleterious mutation in BRCA2. The spect rum of mutations was unique in that one novel BRCA1 mutation (1625del5) and three novel BRCA2 mutations (1536del4, 6696delTC. and 7795delCT) were iden tified. No recurrent mutations were identified in this cohort, although one BRCA2 (2816insA) mutation had been previously reported. In addition, two B RCA1 and four BRCA2 missense mutations of unknown significance were identif ied, one of which was novel. Taken together with our previous report on rec urrent mutations seen in unrelated families, we conclude that African Ameri cans have a unique mutation spectrum in BRCA1 and BRCA2 genes, but recurren t mutations are likely to be more widely dispersed and therefore not readil y identifiable in this population.