van Kempen Léon C, Redpath Margaret, Robert Caroline, Spatz Alan
McGill University, Montreal, QC, Canada.
Lady Davis Institute for Medical Research, Montreal, QC, Canada.
Melanoma Manag. 2014 Nov;1(2):151-164. doi: 10.2217/mmt.14.23. Epub 2014 Dec 4.
Cutaneous melanoma is associated with strong prognostic phenotypic features, such as gender, Breslow's thickness and ulceration, although the biological significance of these variables is largely unknown. It is likely that these features are surrogates of important biological events rather than directly promoting cutaneous melanoma progression. In this article, we address the molecular mechanisms that drive these phenotypic changes. Furthermore, we present a comprehensive overview of recurrent genetic abnormalities, both germline and somatic, in relation to cutaneous melanoma subtypes, ultraviolet exposure and anatomical localization, as well as pre-existing and targeted therapy-induced mutations that may contribute to resistance. The increasing knowledge of critically important oncogenes and tumor-suppressor genes is promoting a transition in melanoma diagnosis, in which single-gene testing will be replaced by multiplex and multidimensional analyses that combine classical histopathological characteristics with the molecular profile for the prognostication and selection of melanoma therapy.
皮肤黑色素瘤与一些强大的预后表型特征相关，如性别、 Breslow厚度和溃疡形成，尽管这些变量的生物学意义在很大程度上尚不清楚。这些特征很可能是重要生物学事件的替代指标，而非直接促进皮肤黑色素瘤进展。在本文中，我们阐述了驱动这些表型变化的分子机制。此外，我们全面概述了与皮肤黑色素瘤亚型、紫外线暴露和解剖定位相关的复发性遗传异常，包括种系和体细胞异常，以及可能导致耐药性的既往存在的和靶向治疗诱导的突变。对至关重要的癌基因和肿瘤抑制基因的认识不断增加，正在推动黑色素瘤诊断的转变，其中单基因检测将被多重和多维分析所取代，这些分析将经典组织病理学特征与分子谱相结合，用于黑色素瘤治疗的预后评估和选择。
