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DNA hypomethylation and hemimethylation in cancer.
MedLine Citation:
PMID:  22956495     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
In contrast to earlier views that there was much compartmentalization of the types of sequences subject to cancer-linked changes in DNA epigenetics, it is now clear that both cancer-associated DNA hypomethylation and hypermethylation are found throughout the genome. The hypermethylation includes promoters of tumor suppressor genes whose expression becomes repressed, thereby facilitating cancer formation. How hypomethylation contributes to carcinogenesis has been less clear. Recent insights into tissue-specific intra- and intergenic methylation and into cancer methylomes suggest that some of the DNA hypomethylation associated with cancers is likely to aid in tumor formation and progression by many different pathways, including effects on transcription in cis. Cancer-associated loss of DNA methylation from intergenic enhancers, promoter regions, silencers, and chromatin boundary elements may alter transcription rates. In -addition, cancer-associated intragenic DNA hypomethylation might modulate -alternative promoter usage, -production of intragenic noncoding RNA transcripts, cotranscriptional splicing, and transcription initiation or elongation. Initial studies of hemimethylation of DNA in cancer and many new studies of DNA demethylation in normal tissues suggest that active demethylation with spreading of hypomethylation can explain much of the cancer-associated DNA hypomethylation. The new discoveries that genomic 5-hydroxymethylcytosine is an intermediate in DNA demethylation, a base with its own functionality, and a modified base that, like 5-methylcytosine, exhibits cancer-associated losses, suggest that both decreased hydroxymethylation and decreased methylation of DNA play important roles in carcinogenesis.
Authors:
Melanie Ehrlich; Michelle Lacey
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Advances in experimental medicine and biology     Volume:  754     ISSN:  0065-2598     ISO Abbreviation:  Adv. Exp. Med. Biol.     Publication Date:  2013  
Date Detail:
Created Date:  2012-09-07     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0121103     Medline TA:  Adv Exp Med Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  31-56     Citation Subset:  IM    
Affiliation:
Human Genetics Program, Tulane University, New Orleans, LA, 70122, USA, ehrlich9@gmail.com.
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