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.
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Peter MacCallum Canc Ctr, Canc Res Div, Melbourne, Vic, Australia
Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Vic, AustraliaPeter MacCallum Canc Ctr, Canc Res Div, Melbourne, Vic, Australia
Michalak, Ewa M.
Burr, Marian L.
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Peter MacCallum Canc Ctr, Canc Res Div, Melbourne, Vic, Australia
Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Vic, Australia
Univ Cambridge, Cambridge Inst Med Res, Cambridge, EnglandPeter MacCallum Canc Ctr, Canc Res Div, Melbourne, Vic, Australia
Burr, Marian L.
Bannister, Andrew J.
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Univ Cambridge, Curdon Inst & Dept Pathol, Cambridge, EnglandPeter MacCallum Canc Ctr, Canc Res Div, Melbourne, Vic, Australia
Bannister, Andrew J.
Dawson, Mark A.
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Peter MacCallum Canc Ctr, Canc Res Div, Melbourne, Vic, Australia
Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Vic, Australia
Univ Melbourne, Ctr Canc Res, Melbourne, Vic, AustraliaPeter MacCallum Canc Ctr, Canc Res Div, Melbourne, Vic, Australia