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....

Full description

Bibliographic Details
Main Author: Gerd P. Pfeifer
Format: Article
Language:English
Published: MDPI AG 2018-04-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:http://www.mdpi.com/1422-0067/19/4/1166
id doaj-10880707588b4f8c890c8e02d72d6b8e
record_format Article
spelling 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
collection 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
_version_ 1716748792327307264