Department of Dermatology, University Hospitals Leuven, 3000 Leuven, Belgium.
Department of Imaging and Pathology, Translational Cell and Tissue Research, University Hospitals Leuven, 3000 Leuven, Belgium.
Int J Mol Sci. 2021 Oct 1;22(19):10674. doi: 10.3390/ijms221910674.
Loss-of-function events in tumor suppressor genes (TSGs) contribute to the development and progression of cutaneous malignant melanoma (CMM). Epigenetic alterations are the major mechanisms of TSG inactivation, in particular, silencing by promoter CpG-island hypermethylation. TSGs are valuable tools in diagnosis and prognosis and, possibly, in future targeted therapy. The aim of this narrative review is to outline bona fide TSGs affected by promoter CpG-island hypermethylation and their functional role in the progression of CMM. We conducted a systematic literature review to identify studies providing evidence of bona fide TSGs by cell line or animal experiments. We performed a broad first search and a gene-specific second search, supplemented by reference checking. We included studies describing bona fide TSGs in CMM with promoter CpG-island hypermethylation in which inactivating mechanisms were reported. We extracted data about protein role, pathway, experiments conducted to meet the bona fide criteria and hallmarks of cancer acquired by TSG inactivation. A total of 24 studies were included, describing 24 bona fide TSGs silenced by promoter CpG-island hypermethylation in CMM. Their effect on cell proliferation, apoptosis, growth, senescence, angiogenesis, migration, invasion or metastasis is also described. These data give further insight into the role of TSGs in the progression of CMM.
肿瘤抑制基因（TSGs）的失活事件导致皮肤恶性黑色素瘤（CMM）的发生和发展。表观遗传改变是 TSG 失活的主要机制，特别是启动子 CpG 岛过度甲基化导致的沉默。TSGs 是诊断和预后的有价值的工具，并且可能在未来的靶向治疗中具有价值。本综述的目的是概述受启动子 CpG 岛过度甲基化影响的真正 TSGs 及其在 CMM 进展中的功能作用。我们进行了系统的文献综述，以确定通过细胞系或动物实验提供真正 TSG 证据的研究。我们进行了广泛的首次搜索和特定基因的第二次搜索，并通过参考文献检查进行了补充。我们纳入了描述 CMM 中具有启动子 CpG 岛过度甲基化的真正 TSGs 的研究，其中报道了失活机制。我们提取了有关蛋白质作用、途径、为满足真正标准而进行的实验以及 TSG 失活获得的癌症标志的数据。共纳入 24 项研究，描述了 24 个受 CMM 中启动子 CpG 岛过度甲基化沉默的真正 TSGs。还描述了它们对细胞增殖、凋亡、生长、衰老、血管生成、迁移、侵袭或转移的影响。这些数据进一步深入了解了 TSG 在 CMM 进展中的作用。
