Article

Integrated profiling reveals a global correlation between epigenetic and genetic alterations in mesothelioma.

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.
Cancer Research (impact factor: 7.86). 07/2010; 70(14):5686-94. DOI:10.1158/0008-5472.CAN-10-0190
Source: PubMed

ABSTRACT 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.

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Keywords

asbestos exposure
 
associated genes
 
CN alteration extent
 
combined contributions
 
correlated CN
 
correlated CN alteration
 
discrete correlations
 
DNA methylation profile
 
DNA methylation profiles
 
DNA methyltransferase gene DNMT1
 
findings define
 
gene copy number
 
gene inactivation
 
global epigenetic dysregulation
 
methylation profile classes
 
pleural mesotheliomas
 
prevalent allele loss
 
strong association
 
tumor CN alteration
 
two genes