CDKN2A mutations in a Greek cohort of melanoma patients with indication for genetic test: correlation with other malignancies

Background: Although germline mutations in CDKN2A gene account for just 1-2% of sporadic melanoma cases, their carriage increases significantly in the case of familial melanoma (FM) and/or multiple primary melanoma (MPM) patients.Furthermore, carriers of CDKN2A class 4-5 (likely pathogenic/pathogenic) variants are also at increased risk for developing other malignancies, such as pancreatic cancer.Relevant data in the Greek population are lacking.The aim of this study was to evaluate the presence of pancreatic cancer and other malignancies and to correlate it with CDKN2A status in a Greek cohort of melanoma patients with indication for genetic test.Methods: A total of 189 melanoma patients (94 men and 95 women) with indication for CDKN2A genetic test were included in the study.CDKN2A variations were analyzed using targeted sequencing.Information on other cancers was extracted from the medical records of all participants.Results: The cohort included 107 patients with melanoma and family history of melanoma, 4 patients with melanoma and family history of both melanoma and pancreatic cancer, 22 patients with MPM and family history of melanoma, 46 patients with MPM only, and 10 with melanoma and family history of pancreatic cancer.42/ 189 (22.2%) patients (24 with FM, 15 with both family history and MPM, and 3 with only MPM) harbored class 4-5 variants for CDKN2A.The mean age of melanoma diagnosis was 42 years for the CDKN2A carriers versus 50.8 years for the non-carriers.7/42 (16.7%) of the carriers had also a personal history of cancer other than melanoma, whereas 12/147 (8.2 %) of the rest of the patients had been diagnosed with another type of cancer.Regarding family history of pancreatic cancer, 3/4 (75%) patients who also had family history of melanoma were CDKN2A carriers, whereas no patient with family history of pancreatic cancer without FM harbored CDKN2A mutations.Conclusions: CDKN2A carriage in our cohort was associated with an increased risk for other cancers, further supporting the value of genetic testing as well as the need for enhanced oncologic surveillance in this patient population.Family history of pancreatic cancer without family history of melanoma was not associated with CDKN2A mutations in our cohort.Large studies incorporating data from various populations with different genetic background will be essential to determine the associated risks and establish appropriate guidelines for optimal patient management.