The genetic determinants of melanoma
Melanoma, the most dangerous form of skin cancer, is usually caused by damage to the skin cell DNA by ultraviolet (UV) radiation from the Sun. Apart from UV-mediated genetic alterations, researchers have started to explore the possibility that certain inherited gene variations may predispose individuals to melanoma development. The ultimate aim of the EU-funded ‘Genetic and environmental determinants of melanoma: translation into behavioural change’ (Genomel) project was to investigate the genetic and environmental risk factors for melanoma by identifying melanoma susceptibility genes and their variations in melanoma patients. For this purpose, a large European network was built that focused on developing joint data collection for gene-environment interaction studies. After collecting biological samples and sharing resources, the consortium performed genome-wide analysis of sporadic and familial melanomas. Three loci on chromosomes 9, 11 and 16 were found to be replicated among tumours. Two of these loci correlated with the tyrosinase (TYR) and melanocortin-1 receptor (MC1R) genes previously found to be associated with skin pigmentation and sun sensitivity. Additional microarray analysis of genetic polymorphisms associated with melanoma led to the identification of critical sequence variants of the replicated chromosomal loci and of CDKN2A, a cell-cycle regulator gene frequently altered in melanoma. Scientists performed an overall comprehensive investigation of somatic genomic events in CDKN2A-mutated melanomas alongside an exploration of the role of newly identified melanoma susceptibility genes. The role of the environment – in terms of sun exposure – in melanoma formation was also investigated as well as its potential interaction with known susceptibility genes. An ambitious programme of online research and dissemination accompanied the Genomel consortium's genetic and epidemiological research. The Genomel website facilitated this health education to prevent melanoma through appropriate strategies for sun protection and early detection linked to risk estimation.
