Global RNA Expression and DNA Methylation Patterns in Primary Anaplastic Thyroid Cancer

被引:23
|
作者
Ravi, Naveen [1 ]
Yang, Minjun [1 ]
Mylona, Nektaria [2 ,3 ]
Wennerberg, Johan [3 ,4 ]
Paulsson, Kajsa [1 ]
机构
[1] Lund Univ, Div Clin Genet, Dept Lab Med, SE-22185 Lund, Sweden
[2] Lund Univ, Div Oncol & Pathol, Clin Sci, SE-22185 Lund, Sweden
[3] Skane Univ Hosp, SE-22185 Lund, Sweden
[4] Lund Univ, Div Otorhinolaryngol Head & Neck Surg, Clin Sci, SE-22185 Lund, Sweden
基金
瑞典研究理事会;
关键词
anaplastic thyroid cancer; DNA methylation; RNA sequencing; formalin-fixed paraffin-embedded tissue; SIGNALING PATHWAY; GENE-EXPRESSION; IDENTIFICATION; PAPILLARY; INVASION; TARGET; MAGI1;
D O I
10.3390/cancers12030680
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 MTOR, NOTCH1, and MAGI1. Furthermore, TSHR and SLC26A7, 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.
引用
收藏
页数:11
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