Journal
DIGESTIVE DISEASES AND SCIENCES
Volume 63, Issue 8, Pages 2059-2069Publisher
SPRINGER
DOI: 10.1007/s10620-018-5090-8
Keywords
Barrett's esophagus; Esophageal adenocarcinoma; Cancer genomics; LOH; Aneuploidy; Genomic instability; DNA methylation
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Funding
- National Institutes of Health (NIH) National Cancer Institute (NCI) [RO1CA115513, P30CA15704, UO1CA152756, U54CA143862, P01CA077852]
- DeGregorio Family Foundation
- Lattner Family Foundation
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Esophageal adenocarcinoma (EAC) develops from Barrett's esophagus (BE), a condition where the normal squamous epithelia is replaced by specialized intestinal metaplasia in response to chronic gastroesophageal acid reflux. In a minority of individuals, BE can progress to low- and high-grade dysplasia and eventually to intra-mucosal and then invasive carcinoma. BE provides researchers with a unique model to characterize the process by which a carcinoma arises from its precursor lesion. Molecular studies of BE have demonstrated that it is not simply a metaplastic tissue, but rather it harbors frequent alterations that are also present in dysplastic BE and in EAC. Both BE and EAC are characterized by loss of heterozygosity, aneuploidy, specific genetic mutations, and clonal diversity. Epigenetic abnormalities, primary alterations in DNA methylation, are also frequently seen in BE and EAC. Candidate gene and array-based approaches have demonstrated that numerous tumor suppressor genes exhibit aberrant promoter methylation, and some of these altered genes are associated with the neoplastic progression of BE. It has also been shown that the BE and EAC epigenomes are characterized by hypomethylation of intragenic and non-coding regions Recent studies have also provided new insight into the evolutionary forces underlying the molecular alterations seen in BE and EAC and into the molecular pathogenesis of EAC.
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