Fu Siqi, Wu Haijing, Zhang Huiming, Lian Christine G, Lu Qianjin
Department of Dermatology, Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Medical Epigenomics, Changsha, Hunan, China.
Program in Dermatopathology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Oncotarget. 2017 May 30;8(44):78163-78173. doi: 10.18632/oncotarget.18293. eCollection 2017 Sep 29.
Melanoma is a malignant tumor of melanocytes and is considered to be the most aggressive cancer among all skin diseases. The pathogenesis of melanoma has not been well documented, which may restrict the research and development of biomarkers and therapies. To date, several genetic and epigenetic factors have been identified as contributing to the development and progression of melanoma. Besides the findings on genetic susceptibilities, the recent progress in epigenetic studies has revealed that loss of the DNA hydroxymethylation mark, 5-hydroxymethylcytosine (5-hmC), along with high levels of DNA methylation at promoter regions of several tumor suppressor genes in melanoma, may serve as biomarkers for melanoma. Moreover, 5-Aza-2'-deoxycytidine, an epigenetic modifier causing DNA demethylation, and ten-eleven translocation family dioxygenase (TET), which catalyzes the generation of 5-hmC, demonstrate therapeutic potential in melanoma treatment. In this review, we will summarize the latest progress in research on DNA methylation/hydroxymethylation in melanoma, and we will discuss and provide insight for epigenetic biomarkers and therapies for melanoma. Particularly, we will discuss the role of DNA hydroxymethylation in melanoma infiltrating immune cells, which may also serve as a potential target for melanoma treatment.
黑色素瘤是一种黑素细胞恶性肿瘤，被认为是所有皮肤疾病中侵袭性最强的癌症。黑色素瘤的发病机制尚未有充分记载，这可能会限制生物标志物和治疗方法的研发。迄今为止，已确定有几种遗传和表观遗传因素促成黑色素瘤的发生和发展。除了遗传易感性方面的发现外，表观遗传学研究的最新进展表明，DNA羟甲基化标记5-羟甲基胞嘧啶（5-hmC）的缺失，以及黑色素瘤中几个肿瘤抑制基因启动子区域高水平的DNA甲基化，可能作为黑色素瘤的生物标志物。此外，引起DNA去甲基化的表观遗传修饰剂5-氮杂-2'-脱氧胞苷和催化5-hmC生成的十一锌指家族双加氧酶（TET）在黑色素瘤治疗中显示出治疗潜力。在这篇综述中，我们将总结黑色素瘤中DNA甲基化/羟甲基化研究的最新进展，并对黑色素瘤的表观遗传生物标志物和治疗方法进行讨论并提供见解。特别是，我们将讨论DNA羟甲基化在黑色素瘤浸润免疫细胞中的作用，这也可能成为黑色素瘤治疗的潜在靶点。
