Genetics of melanoma predisposition
The melanoma research group has a longstanding interest in the genetic aspects of familial melanoma, also known as familial atypical multiple mole-melanoma syndrome (FAMMM). Familial melanoma is an example of a disorder in which gene-environment interactions play a crucial role in addition to heritable genetic alterations. Studies on a large collection of families with multiple melanoma cases in The Netherlands demonstrated that 80% of them had a founder mutation in the CDKN2A gene (p16-Leiden mutation). This tumor suppressor gene encodes for the p16 and p14 proteins that are primarily involved in cell cycle regulation. The highly variable risk for p16-Leiden mutation carriers to develop melanoma suggests a role for other genetic and environmental factors. These are the subject of current research, which is mostly performed through participation in the international melanoma genetics consortium GenoMEL (www.genomel.org). In our search to identify melanoma-predisposing genetic variants we also focus on large sporadic melanoma case-control cohorts. SNP-based genome wide approaches have identified genomic loci that are primarily related to genes in pigmentation pathways. We are involved in validation of these SNPs in additional cohorts and functional analysis of genetic variants in relation to melanoma progression.
MC1R & oxidative stress management
Epigenetics of melanoma
Melanoma skin model
The department has the largest pigmented lesion clinic in The Netherlands and serves as a tertiary referral center for (familial) melanoma. The well-organized management of patients with dysplastic naevi and melanoma ensures the availability of clinically annotated patient material for research purposes and the possibility for clinical ‘translation’ of research findings. The special position of our clinic as a melanoma center in The Netherlands is related to a large population of patients with familial melanoma carrying the p16-Leiden mutation living in the vicinity of Leiden. Optimizing the management of patients predisposed to the development of melanoma is one of the goals of our research group. To this end epidemiological studies of genetic and environmental influences on melanoma risk are performed and application of imaging devices in the early diagnosis of melanoma is studied by clinical researchers attached to our department.
Figure 1: Shown is cross section of a melanoma skin model. In figure 1A the invasive behaviour of melanoma is mimicked in a human skin model using a cell line. These invasive cells have a high proliferative capacity (brown coloured cells stained for protein ki67) as shown in figure 1B