Document Detail


Integrated profiling reveals a global correlation between epigenetic and genetic alterations in mesothelioma.
MedLine Citation:
PMID:  20587528     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Development of mesothelioma is linked mainly to asbestos exposure, but the combined contributions of genetic and epigenetic alterations are unclear. We investigated the potential relationships between gene copy number (CN) alterations and DNA methylation profiles in a case series of pleural mesotheliomas (n = 23). There were no instances of significantly correlated CN alteration and methylation at probed loci, whereas averaging loci over their associated genes revealed only two genes with significantly correlated CN and methylation alterations. In contrast to the lack of discrete correlations, the overall extent of tumor CN alteration was significantly associated with DNA methylation profile when comparing CN alteration extent among methylation profile classes. Further, there was evidence that this association was partially attributable to prevalent allele loss at the DNA methyltransferase gene DNMT1. Our findings define a strong association between global genetic and global epigenetic dysregulation in mesothelioma, rather than a discrete, local coordination of gene inactivation.
Authors:
Brock C Christensen; E Andres Houseman; Graham M Poage; John J Godleski; Raphael Bueno; David J Sugarbaker; John K Wiencke; Heather H Nelson; Carmen J Marsit; Karl T Kelsey
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-06-29
Journal Detail:
Title:  Cancer research     Volume:  70     ISSN:  1538-7445     ISO Abbreviation:  Cancer Res.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-07-16     Completed Date:  2010-08-24     Revised Date:  2013-07-19    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5686-94     Citation Subset:  IM    
Copyright Information:
(c)2010 AACR.
Affiliation:
Departments of Pathology and Laboratory Medicine, Community Health, Center for Environmental Health and Technology, and Molecular Pharmacology and Physiology, Brown University, Providence, Rhode Island 02903, USA.
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MeSH Terms
Descriptor/Qualifier:
Alleles
DNA (Cytosine-5-)-Methyltransferase / genetics
DNA Methylation
Epigenesis, Genetic
Gene Dosage
Gene Expression Profiling
Humans
Mesothelioma / enzymology,  genetics*
Pilot Projects
Pleural Neoplasms / enzymology,  genetics*
Polymorphism, Single Nucleotide
Grant Support
ID/Acronym/Agency:
R01 CA100679/CA/NCI NIH HHS; R01 CA100679-08/CA/NCI NIH HHS; R01 CA126939/CA/NCI NIH HHS; R01 CA126939-04/CA/NCI NIH HHS; R01CA100679/CA/NCI NIH HHS; R01CA126939/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
EC 2.1.1.37/DNA (Cytosine-5-)-Methyltransferase; EC 2.1.1.37/DNA (cytosine-5-)-methyltransferase 1
Comments/Corrections

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