Monitoring Changes in Age and Diagnostic Severity of Melanoma Patients from 2005 to 2023: A Single-Center Experience

about mutational landscape in cutaneous melanoma and pancreatic cancer, focusing on similarities of these two apparently so different tumors in terms of site, type of cell involved, and embryonic origin.The familial forms of cutaneous melanoma and pancreatic cancers are often characterized by a common mutated gene, namely CDKN2A.In fact, a germline mutation in CDKN2A gene can be responsible for the development of the familial atypical multiple mole and melanoma syndrome (FAMMM), which is characterized by melanomas and pancreatic cancer development.On the other hand, sporadic melanoma and pancreatic cancer showed different key driven genes.Methods: The open-access resource cBioPortal has been explored to deepen and investigate the common mutational landscape of these two tumors.We investigated the common mutated genes found in both melanoma and pancreatic cancer with a frequency of at least 5% of tested patients and copy number alterations with a frequency of at least of 3%.Results: Data showed that 18 mutated genes and 3 copy number alterations are present in both melanoma and pancreatic cancer types.In addition to the thoroughly described CDKN2A, which has been found in melanoma and pancreatic cancer with the same frequence (9.4%) in AACR Project GENIE registry, data showed other interestingly and relevant genes, since they were profiled in many samples (more than 900 samples for both groups) and found highly mutated.First, there is TP53 that is one of the most frequently mutated gene in cancer.Another gene that is often mutated in several cancers is LRP1B, specifically, this gene is frequently inactivated at both genetic and epigenetic levels.27% of melanomas and 7% of pancreatic cancers in GENIE cohort showed mutation in KMT2D gene, also known as Mixed-lineage leukemia protein 4 (MLL4).Other four genes showed a frequency between 5-15% in a large number of tested melanoma and pancreatic cancer samples, namely ARID1A, PDE4DIP, PRKDC and RANBP2.Conclusions: Our work gives valuable insights into the genetic underpinnings of melanoma and pancreatic cancer, urging the continued exploration and research of new genetic biomarkers able to identify patients and families at high-risk of developing both cancers and to address to screening and to an effective clinical management of the patient.