Germline mutations of the BRCA1 and BRCA2 genes in a breast and ovarian cancer patient

A patient with breast carcinoma diagnosed at the age of 30 years and ovarian carcinoma diagnosed at the age of 41 years was found to have germline mutations in both the BRCA1 and the BRCA2 genes. The patient was of Ashkenazi Jewish descent and the BRCA2 mutation was 6174delT, known to be very common in this population. The BRCA1 mutation, however, was 3888delGA, a mutation not previously reported in this ethnic group. The patient's breast cancer exhibited loss of heterozygosity (LOH) at the BRCA1 locus but not at BRCA2, and her ovarian cancer sustained LOH at BRCA1 and BRCA2. The BRCA1 mutation originated from patient's father, who had no personal or family history of cancer. The patient's mother, who was found to carry the BRCA2 mutation, was affected by late-onset breast cancer and her tumor exhibited LOH at BRCA2. These findings indicate that compound heterozygotes for germline mutations of BRCA1 and BRCA2 exist and may be expected to develop normally and that either gene may contribute to breast or ovarian cancer development in such individuals. The implications of this case in regard to genetic testing and counseling are also substantial.