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5. GenoMEL Consortium. Association of MC1R variants and host phenotypes with melanoma risk in CDKN2A mutation carriers: a GenoMEL study. J Natl Cancer Inst 2010; 102: 1568-83. 6. Gao L, van Nieuwpoort FA, Out-Luiting JJ, et al. Genome-wide analysis of gene and protein expression of dysplastic naevus cells. J Skin Cancer 2012; 2012: 981308. 7. Doorn R van, Zoutman WH, Gruis NA. Absence of germline epimutation of the CDKN2A gene in familial melanoma. J Invest Dermatol 2009; 129: 781-4. 8. Rhee JI van der, de Snoo FA, Vasen HF, et al. Effectiveness and causes for failure of surveillance of CDKN2A-mutated melanoma families. J Am Acad Dermatol 2011; 65: 289-96. 9. Rhee JI van der, Krijnen P, Gruis NA, et al. Clinical and histologic characteristics of malignant melanoma in families with a germline mutation in CDKN2A. J Am Acad Dermatol 2011; 65: 281-8. Skin cancer in organ transplant recipients The Department of Dermatology in Leiden has a long tradition of research into non-melanoma skin cancer. In the 70s and 80s Dick Suurmond and Ab Schothorst started this line of research studying photobiology and phototherapy, while Bert Jan Vermeer continued this line with photoimmunology. In 1985 Jan Nico Bouwes Bavinck started research in organ transplant among recipients, who fre- quently develop skin cancers.[1] Several studies report a cumulative incidence of 10% at 10 years up to 40% at 20 years after transplantation.[2] Clinical and epidemiological studies were focused parti- cularly on risk factors for skin cancer in organ transplant recipients, and in 1992 Jan Nico Bouwes Bavinck defended his PhD thesis on this topic. In the last two decades these studies, which were performed in close collaboration with other departments within the LUMC, across the Netherlands and world-wide (http://www.scopenetwork.org/ and http://www.itscc.org/), identified many risk factors including the immunosuppressive therapy, exposure to UV light, smoking, human papilloma virus (HPV) infection, and genetic factors, such as HLA phenotype and polymorphisms in the melanocortin 1 receptor (MC1R) gene.[3,4,5] Several clinical trials were performed. It was shown that acitretin was effective in reducing the number of skin cancers, but photodynamic therapy and switching the immunosuppressive regimen to rapamycine were less effective.[6] Curettage followed by electrocoagulation was shown to be an effective treatment of selected squamous-cell carcinomas. In 2001 Frank de Gruijl joined the Leiden group and clinical and epidemiological studies were supplemented with fundamental studies in mice, cell cultures and in vitro skin models. These studies focused on early UV-driven carcinogenic events (DNA damage and mutations in the P53 tumour- suppressor gene) and modulation thereof by immunosuppressants and by HPV.[7,8,9] Additionally, patient material was analyzed to retrace the putative pathogenic steps of tumour formation, and tumour explants and cell lines were introduced into in vitro skin models to study tumour growth and invasion. Recent studies supported by grants from the Dutch Cancer Foundation focused on the role of stem cells.[10] It was found that quiescent stem cells can accumulate DNA damage at low UV dosages and thus run an increased mutation risk (e.g., in the p53 gene); at high dosages newly identified actively proliferating stem cells are more likely mutational targets. Their potential conversion to tumour-initiating cells would make them prime targets for preventive and therapeutic intervention. 90 BWEADVSMGFINCORR:Opmaak 1 21-07-2014 17:40 Pagina 90