title: DNA methylation profiling in Barrett's esophagus and esophageal adenocarcinoma reveals unique methylation signatures and molecular subclasses.
abstract: 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.affiliation: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. akaz@fhcrc.org
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Kaz
authors.forename: Chao-Jen
authors.initials: CJ
authors.lastname: Wong
authors.forename: Yanxin
authors.initials: Y
authors.lastname: Luo
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Virgin
authors.forename: M Kay
authors.initials: MK
authors.lastname: Washington
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Willis
authors.forename: Rom S
authors.initials: RS
authors.lastname: Leidner
authors.forename: Amitabh
authors.initials: A
authors.lastname: Chak
authors.forename: William M
authors.initials: WM
authors.lastname: Grady
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000368:Aged; D001471:Barrett Esophagus / Q000235:genetics* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000235:genetics; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D018450:Disease Progression; D044127:Epigenesis, Genetic / Q000235:genetics; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011379:Prognosis; D017422:Sequence Analysis, DNA
chemical_list: D014408:Biomarkers, Tumor