Double heterozygosity for germline mutations in BRCA1 and p53 in a woman with early onset breast cancer

To report on a highly unusual case of a 20-year-old woman who presented with multifocal metaplastic breast cancer and was subsequently found to carry deleterious germline mutations in both BRCA1 and p53. Genetic testing was requested on an expedited basis to assist in surgical decision-making and BRCA1/2 and p53 genetic analysis was ordered concurrently. BRCA1/2 and p53 analyses were completed using a combination of direct DNA sequencing and multiplex ligation probe amplification (MLPA). The patient was found to carry a deletion of exon 3 of the BRCA1 gene and a splice site mutation at the exon4/intron4 boundary of the p53 gene. To our knowledge, this is the first report of double heterozygosity in BRCA1 and p53. The patient’s clinical presentation is highly reminiscent of that predicted by preclinical mouse models. In patients with early onset breast cancer, the possibility of germline mutations in more than one cancer susceptibility gene should be considered. This could have important clinical implications for patients and their at-risk family members.