Melanoma research group

Cutaneous melanoma is a malignant tumor derived from melanocytes residing in the skin. Due to its metastatic propensity melanoma is associated with significant mortality. Clinically melanoma needs to be distinguished from melanocytic nevus, a benign lesion composed of melanocytes in a stable growth arrest. Causative genetic lesions and resulting cell signaling alterations driving melanoma development have been identified, which has enabled targeted treatment. In addition, insights into tumor-immune interaction in melanoma have led to the development of immunotherapeutic approaches for patients with metastatic disease. Approximately 10% of patients with melanoma have a positive family history for this malignancy. The genetic basis of melanoma susceptibility is complex. CDKN2A is the major hereditary melanoma gene; inactivating gene variants are identified in more than 30% of melanoma families. Carriers have a lifetime risk of 70% to develop melanoma and are at increased risk of pancreatic cancer and other tumor types.

Several clinical and preclinical departments are involved in melanoma research and patient care at LUMC. There are strong collaborations with Antoni van Leeuwenhoek-Netherlands Cancer Institute and other melanoma centers in the Netherlands. The department of dermatology has the largest pigmented lesion clinic in the Netherlands. LUMC is a national expertise center and a European Reference Center for familial melanoma. The special position of our clinic as a melanoma center in the Netherlands is also related to a large population of patients with hereditary melanoma due to a CDKN2A gene variant living in the vicinity of Leiden.

Basal and translational studies

The melanoma research group is embedded in the Cell and Chemical Biology laboratories and actively participates in the Leiden Center for Computational Oncology. This allows the application of sophisticated molecular biological and omics technologies. An overall aim is to advance understanding of the molecular alterations occurring in early stages of melanocytic tumorigenesis, to identify targets for prevention and therapy that improve the management of patients at increased risk of melanoma.
Congenital melanocytic nevi and dysplastic nevi in patients with hereditary melanoma carry a substantial risk of malignant transformation. To prevent melanoma development from these precursor lesions we are exploring pharmacological and immunological approaches to eliminate melanocytic nevi, lesions composed of melanocytes in a state of oncogene-induced senescence. CDKN2A is a critical tumor suppressor gene as well as a susceptibility gene for melanoma. This gene located on chromosome 9p21 encodes for the p16 and p14 proteins. The functions of CDKN2A, the consequences of its inactivation in melanoma and potential associated therapeutic vulnerabilities are studied using omics methodology. The research groups employs melanocyte cell systems, 3D skin organoid models, spatial methods to characterize the tumor immune microenvironment, computational and screening methodologies.

Clinical, genetic and image analysis studies

The well-organized management of patients at increased risk of melanoma ensures the availability of clinically annotated patient material for research purposes and the possibility for clinical translation of research findings. To optimize the management of patients at increased risk of developing melanoma is a central aim of our studies. An important goal is to further our understanding of the genetic basis of familial occurrence of melanoma, studied in collaboration with the department of Clinical Genetics. The department participates in genetic epidemiological studies in patients with hereditary melanoma due to CDKN2A and BAP1 gene variants in European and global consortia. In addition, skin imaging technology and deep learning image analysis in the early diagnosis of melanoma are studied.