Document Detail


DNA methylation profiling in Barrett's esophagus and esophageal adenocarcinoma reveals unique methylation signatures and molecular subclasses.
MedLine Citation:
PMID:  22139570     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Barrett's esophagus (BE) is a metaplastic process whereby the normal stratified, squamous esophageal epithelium is replaced by specialized intestinal epithelium. Barrett's is the only accepted precursor lesion for esophageal adenocarcinoma (EAC), a solid tumor that is rapidly increasing in incidence in western countries. BE evolves into EAC through intermediate steps that involve increasing degrees of dysplasia. Current histologic criteria are quite subjective and the clinical behavior of BE is highly variable and difficult to predict using these standards. It is widely believed that molecular alterations present in BE and EAC will provide more precise prognostic and predictive markers for these conditions than the current clinical and histologic features in use. In order to further define molecular alterations that can classify unique groups of BE and EAC, we utilized methylation microarrays to compare the global gene methylation status of a collection of normal squamous, BE, BE + high-grade dysplasia (HGD), and EAC cases. We found distinct global methylation signatures, as well as differential methylation of specific genes, that discriminated these histological groups. We also noted high and low methylation epigenotypes among the BE and EAC cases. Additional validation of those CpG sites that distinguished BE from BE + HGD and EAC may lead to the discovery of useful biomarkers with potential clinical applications in the diagnosis and prognosis of BE and EAC.
Authors:
Andrew M Kaz; Chao-Jen Wong; Yanxin Luo; Jeffrey B Virgin; M Kay Washington; Joseph E Willis; Rom S Leidner; Amitabh Chak; William M Grady
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Epigenetics : official journal of the DNA Methylation Society     Volume:  6     ISSN:  1559-2308     ISO Abbreviation:  Epigenetics     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-12-05     Completed Date:  2012-04-02     Revised Date:  2013-07-31    
Medline Journal Info:
Nlm Unique ID:  101265293     Medline TA:  Epigenetics     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1403-12     Citation Subset:  IM    
Affiliation:
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. akaz@fhcrc.org
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MeSH Terms
Descriptor/Qualifier:
Adenocarcinoma / genetics*,  pathology
Aged
Barrett Esophagus / genetics*,  pathology
CpG Islands / genetics*
DNA Methylation / genetics*
Disease Progression
Epigenesis, Genetic / genetics
Esophageal Neoplasms / genetics*,  pathology
Gene Expression Regulation, Neoplastic
Humans
Middle Aged
Neoplasm Staging
Oligonucleotide Array Sequence Analysis / methods
Prognosis
Sequence Analysis, DNA
Tumor Markers, Biological / genetics
Grant Support
ID/Acronym/Agency:
05K08-DK080630/DK/NIDDK NIH HHS; CA135692/CA/NCI NIH HHS; K24DK002800/DK/NIDDK NIH HHS; P30 CA015704/CA/NCI NIH HHS; U01 CA152756/CA/NCI NIH HHS; U01CA152756-01/CA/NCI NIH HHS; U54 CA163060/CA/NCI NIH HHS; U54 CA163060-01/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Tumor Markers, Biological
Comments/Corrections

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