Defining Driver DNA Methylation Changes in Human Cancer
Human malignant tumors are characterized by pervasive changes in the patterns of DNA methylation. These changes include a globally hypomethylated tumor cell genome and the focal hypermethylation of numerous 5′-cytosine-phosphate-guanine-3′ (CpG) islands, many of them associated with gene promoters....
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Online Access: | http://www.mdpi.com/1422-0067/19/4/1166 |
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doaj-10880707588b4f8c890c8e02d72d6b8e2020-11-24T21:13:34ZengMDPI AGInternational Journal of Molecular Sciences1422-00672018-04-01194116610.3390/ijms19041166ijms19041166Defining Driver DNA Methylation Changes in Human CancerGerd P. Pfeifer0Center for Epigenetics, Van Andel Research Institute, 333 Bostwick Avenue NE, Grand Rapids, MI 49503, USAHuman malignant tumors are characterized by pervasive changes in the patterns of DNA methylation. These changes include a globally hypomethylated tumor cell genome and the focal hypermethylation of numerous 5′-cytosine-phosphate-guanine-3′ (CpG) islands, many of them associated with gene promoters. It has been challenging to link specific DNA methylation changes with tumorigenesis in a cause-and-effect relationship. Some evidence suggests that cancer-associated DNA hypomethylation may increase genomic instability. Promoter hypermethylation events can lead to silencing of genes functioning in pathways reflecting hallmarks of cancer, including DNA repair, cell cycle regulation, promotion of apoptosis or control of key tumor-relevant signaling networks. A convincing argument for a tumor-driving role of DNA methylation can be made when the same genes are also frequently mutated in cancer. Many of the most commonly hypermethylated genes encode developmental transcription factors, the methylation of which may lead to permanent gene silencing. Inactivation of such genes will deprive the cells in which the tumor may initiate from the option of undergoing or maintaining lineage differentiation and will lock them into a perpetuated stem cell-like state thus providing an additional window for cell transformation.http://www.mdpi.com/1422-0067/19/4/1166DNA methylationhallmarks of cancer5-methylcytosinecell differentiationgenomic instability |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Gerd P. Pfeifer |
spellingShingle |
Gerd P. Pfeifer Defining Driver DNA Methylation Changes in Human Cancer International Journal of Molecular Sciences DNA methylation hallmarks of cancer 5-methylcytosine cell differentiation genomic instability |
author_facet |
Gerd P. Pfeifer |
author_sort |
Gerd P. Pfeifer |
title |
Defining Driver DNA Methylation Changes in Human Cancer |
title_short |
Defining Driver DNA Methylation Changes in Human Cancer |
title_full |
Defining Driver DNA Methylation Changes in Human Cancer |
title_fullStr |
Defining Driver DNA Methylation Changes in Human Cancer |
title_full_unstemmed |
Defining Driver DNA Methylation Changes in Human Cancer |
title_sort |
defining driver dna methylation changes in human cancer |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2018-04-01 |
description |
Human malignant tumors are characterized by pervasive changes in the patterns of DNA methylation. These changes include a globally hypomethylated tumor cell genome and the focal hypermethylation of numerous 5′-cytosine-phosphate-guanine-3′ (CpG) islands, many of them associated with gene promoters. It has been challenging to link specific DNA methylation changes with tumorigenesis in a cause-and-effect relationship. Some evidence suggests that cancer-associated DNA hypomethylation may increase genomic instability. Promoter hypermethylation events can lead to silencing of genes functioning in pathways reflecting hallmarks of cancer, including DNA repair, cell cycle regulation, promotion of apoptosis or control of key tumor-relevant signaling networks. A convincing argument for a tumor-driving role of DNA methylation can be made when the same genes are also frequently mutated in cancer. Many of the most commonly hypermethylated genes encode developmental transcription factors, the methylation of which may lead to permanent gene silencing. Inactivation of such genes will deprive the cells in which the tumor may initiate from the option of undergoing or maintaining lineage differentiation and will lock them into a perpetuated stem cell-like state thus providing an additional window for cell transformation. |
topic |
DNA methylation hallmarks of cancer 5-methylcytosine cell differentiation genomic instability |
url |
http://www.mdpi.com/1422-0067/19/4/1166 |
work_keys_str_mv |
AT gerdppfeifer definingdriverdnamethylationchangesinhumancancer |
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