A mutation found in the BRCA1 or BRCA2 gene of a breast tumor could be either germline or somatically acquired. The prevalence of somatic BRCA1/2 mutations and the ratio between somatic and germline BRCA1/2 mutations in unselected breast cancer patients is currently unclear.

Paired normal and tumor DNA was analyzed for BRCA1/2 mutations by massively parallel sequencing in an unselected cohort of 273 breast cancer patients from south Sweden.

Deleterious germline mutations in BRCA1 (n=10) or BRCA2 (n=10) were detected in 20 patients (7%). Deleterious somatic mutations in BRCA1 (n=4) or BRCA2 (n=5) were detected in 9 patients (3%). Accordingly, about 1 in 9 breast carcinomas (11%) in our cohort harbor a BRCA1/2 mutation. For each gene, the tumor phenotypes were very similar regardless of the mutation being germline or somatically acquired, whereas the tumor phenotypes differed significantly between wildtype and mutated cases. For age at diagnosis, the patients with somatic BRCA1/2 mutations resembled the wildtype patients (median age at diagnosis, germline BRCA1: 41.5 years; germline BRCA2: 49.5 years; somatic BRCA1/2: 65 years; wildtype BRCA1/2: 62.5 years).

In a population without strong germline founder mutations, the likelihood of a BRCA1/2 mutation found in a breast carcinoma being somatic was approximately 1/3, and germline 2/3. This may have implications for treatment and genetic counseling.