Abstracts
Résumé
On estime à environ 5 000 le nombre annuel de nouveaux cas de mélanome en France. La proportion des formes familiales est évaluée, selon les séries, entre 5 % et 10 %. Les aspects cliniques, histologiques et biologiques de progression du mélanome sont actuellement mieux connus ; les développements technologiques récents ont, quant à eux, permis d’aborder les mécanismes moléculaires de la progression tumorale et de mettre en lumière des gènes impliqués dans cette évolution. Toutefois, des difficultés importantes persistent : il existe une grande variabilité dans l’expression de ces gènes, non seulement d’un patient à l’autre, mais aussi selon les stades de la maladie, locaux ou métastatiques ; par ailleurs, certaines des mutations retrouvées au cours du mélanome peuvent également être présentes dans des lésions bénignes (naevus). La variabilité génotypique associée au mélanome rend le ciblage thérapeutique complexe, et constitue actuellement un défi majeur en termes de traitement. Cet article, volontairement non exhaustif, insistera surtout sur les anomalies génomiques les plus étudiées, desquelles semblent naître des perspectives thérapeutiques intéressantes.
Summary
Cutaneous melanoma remains a management challenge. Melanoma is the leading cause of death from skin tumors worldwide. Melanoma progression is well defined in its clinical, histopathological and biological aspects, but the molecular mechanism involved and the genetic markers associated to metastatic dissemination are only beginning to be defined. The recent development of high-throughput technologies aimed at global molecular profiling of cancer is switching on the spotlight at previously unknown candidate genes involved in melanoma. Among those genes, BRAF is one of the most supposed to be of interest and targeted therapies are ongoing in clinical trials. In familial melanoma, germline mutations in two genes, CDKN2A and CDK4, that play a pivotal role in controlling cell cycle and division. It is hope that this better understanding of the biologic features of melanoma and the mechanisms underlying tumor-induced immunosuppression will lead to efficaceous targeted therapy.
Appendices
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