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Global RNA expression and DNA methylation patterns in primary anaplastic thyroid cancer

Ravi, Naveen LU ; Yang, Minjun LU ; Mylona, Nektaria ; Wennerberg, Johan LU orcid and Paulsson, Kajsa LU (2020) In Cancers 12(3).
Abstract

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... (More)

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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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Anaplastic thyroid cancer, DNA methylation, Formalin-fixed paraffin-embedded tissue, RNA sequencing
in
Cancers
volume
12
issue
3
article number
680
publisher
MDPI AG
external identifiers
  • scopus:85081616242
  • pmid:32183222
ISSN
2072-6694
DOI
10.3390/cancers12030680
language
English
LU publication?
yes
id
ddefe3a8-962e-4866-9845-ae8830867484
date added to LUP
2020-04-01 17:17:18
date last changed
2024-05-15 08:36:10
@article{ddefe3a8-962e-4866-9845-ae8830867484,
  abstract     = {{<p>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.</p>}},
  author       = {{Ravi, Naveen and Yang, Minjun and Mylona, Nektaria and Wennerberg, Johan and Paulsson, Kajsa}},
  issn         = {{2072-6694}},
  keywords     = {{Anaplastic thyroid cancer; DNA methylation; Formalin-fixed paraffin-embedded tissue; RNA sequencing}},
  language     = {{eng}},
  month        = {{03}},
  number       = {{3}},
  publisher    = {{MDPI AG}},
  series       = {{Cancers}},
  title        = {{Global RNA expression and DNA methylation patterns in primary anaplastic thyroid cancer}},
  url          = {{http://dx.doi.org/10.3390/cancers12030680}},
  doi          = {{10.3390/cancers12030680}},
  volume       = {{12}},
  year         = {{2020}},
}