BRCA1, BRCA2, TP53, and CDKN2A germline mutations in patients with breast cancer and cutaneous melanoma

Purpose From epidemiological studies it appears that breast cancer (BC) and cutaneous melanoma (CMM) in the same individual occur at a higher frequency than expected by chance. Genetic factors common to both cancers can be suspected. Our goal was to estimate the involvement of ‘‘high risk’ ’ genes in patients presenting these two neo-plasia, selected irrespectively from family history and age at diagnosis. Experimental design Eighty two patients with BC and CMM were screened for BRCA1, BRCA2, TP53, CDKN2A and CDK4 (exon 2) germline mutations. Results Deleterious mutations were identified in 6 pa-tients: two carriers of a BRCA1 germline mutation, two carriers of TP53 germline mutations (one of which also harbored a BRCA2 deleterious mutation, the other one a BRCA2 unclassified variant), and two carriers of a CDKN2A germline mutation. In addition, 6 variants of unknown signification were identified in BRCA1 or BRCA2 genes. Regarding family history, 3/13 (23%) patients with a positive family history of BC or CMM were carriers of a germline mutation, whereas only 3/69 (4%) patients without family history were carriers of a germline mutation. Conclusion Our findings show that few patients with BC and CMM who lacked family histories of these cancers are carriers of deleterious germline mutations in four of the five genes we examined. We describe for the first time, two simultaneous BRCA2 and TP53 mutations, suggesting that analysis in more than one gene could be performed if a patient’s personal or familial history does not match a single syndrome