Ravi Naveen, Yang Minjun, Mylona Nektaria, Wennerberg Johan, Paulsson Kajsa
Department of Laboratory Medicine, Division of Clinical Genetics, Lund University, SE-221 85 Lund, Sweden.
Division of Oncology and Pathology, Clinical Sciences, Lund University and Skåne University Hospital, SE-221 85 Lund, Sweden.
Cancers (Basel). 2020 Mar 13;12(3):680. doi: 10.3390/cancers12030680.
Anaplastic thyroid cancer (ATC) is one of the most malignant tumors, with a median survival of only a few months. The tumorigenic processes of this disease have not yet been completely unraveled. Here, we report an mRNA expression and DNA methylation analysis of fourteen primary ATCs. ATCs clustered separately from normal thyroid tissue in unsupervised analyses, both by RNA expression and by DNA methylation. In expression analysis, enrichment of cell-cycle-related genes as well as downregulation of genes related to thyroid function were seen. Furthermore, ATC displayed a global hypomethylation of the genome but with hypermethylation of CpG islands. Notably, several cancer-related genes displayed a correlation between RNA expression and DNA methylation status, including , and . Furthermore, and , encoding the thyroid-stimulating hormone receptor and an iodine receptor highly expressed in normal thyroid, respectively, displayed low expression as well as aberrant gene body DNA methylation. This study is the largest investigation of global DNA methylation in ATC to date. It shows that aberrant DNA methylation is common in ATC and likely contributes to tumorigenesis in this disease. Future explorations of novel treatments should take this into consideration.
间变性甲状腺癌（ATC）是最恶性的肿瘤之一，中位生存期仅几个月。该疾病的致瘤过程尚未完全阐明。在此，我们报告了对14例原发性ATC的mRNA表达和DNA甲基化分析。在无监督分析中，无论是通过RNA表达还是DNA甲基化，ATC均与正常甲状腺组织分开聚类。在表达分析中，观察到细胞周期相关基因的富集以及甲状腺功能相关基因的下调。此外，ATC表现出基因组整体低甲基化，但CpG岛高甲基化。值得注意的是，几个癌症相关基因在RNA表达和DNA甲基化状态之间显示出相关性，包括 、 和 。此外，分别编码在正常甲状腺中高表达的促甲状腺激素受体和碘受体的 和 ，表现出低表达以及异常的基因体DNA甲基化。这项研究是迄今为止对ATC中全球DNA甲基化的最大规模调查。它表明异常DNA甲基化在ATC中很常见，并且可能促成该疾病的肿瘤发生。未来新型治疗方法的探索应考虑到这一点。
