In this thesis, we performed several genotype and phenotype studies in hereditary and familial melanoma patient cohorts. In the first part, our studies focus on patients with the p16-Leiden founder... Show moreIn this thesis, we performed several genotype and phenotype studies in hereditary and familial melanoma patient cohorts. In the first part, our studies focus on patients with the p16-Leiden founder mutation in the CDKN2A gene. This founder mutation is the major cause of the familial melanoma-pancreatic cancer syndrome in the Dutch population. We studied the cancer phenotype and modifiers of cancer risk in these p16-Leiden mutation carriers. We also evaluated the p16-Leiden pancreatic cancer (PC) surveillance program by studying the role of precursor lesions in the development and early detection of PC, by reflecting on the surgical management of early-stage screen-detected PC and by studying potential biomarkers for the early detection of PC. In the second part of this thesis, our focus shifts to Dutch melanoma families in general, of which ~85% do not harbor a germline CDKN2A mutation. We studied which clinical features are associated with the presence of a CDKN2A mutation in a melanoma family and we created a scoring system to predict CDKN2A mutation probability. Lastly, we genetically characterized melanoma families without a CDKN2A mutation for variants in other (candidate) melanoma predisposition genes. Show less
