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Chromosomal instability and copy number alterations in Barrett’s esophagus and esophageal adenocarcinoma

Paulson, Thomas G. and Maley, Carlo C. and Li, Xiaohong and Li, Hongzhe and Sanchez, Carissa A. and Chao, Dennis L. (2009) Chromosomal instability and copy number alterations in Barrett’s esophagus and esophageal adenocarcinoma. Clinical Cancer Research, 15 (10). pp. 3305-3314. ISSN 1078-0432

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Article URL: http://clincancerres.aacrjournals.org/content/15/1...

Abstract

Purpose: Chromosomal instability, as assessed by many techniques, including DNA content aneuploidy, LOH, and comparative genomic hybridization, has consistently been reported to be common in cancer and rare in normal tissues. Recently, a panel of chromosome instability biomarkers, including LOH and DNA content, has been reported to identify patients at high and low risk of progression from Barrett’s esophagus (BE) to esophageal adenocarcinoma (EA), but required multiple platforms for implementation. Although chromosomal instability involving amplifications and deletions of chromosome regions have been observed in nearly all cancers, copy number alterations (CNAs) in premalignant tissues have not been well characterized or evaluated in cohort studies as biomarkers of cancer risk. Experimental Design: We examined CNAs in 98 patients having either BE or EA using BAC array CGH to characterize CNAs at different stages of progression ranging from early BE to advanced EA. Results: CNAs were rare in early stages (<HGD) but were progressively more frequent and larger in later stages (HGD and EA), including high level amplifications. The number of CNAs correlated highly with DNA content aneuploidy. Patients whose biopsies contained CNAs involving more than 70 Mbp were at increased risk of progression to DNA content abnormalities or EA (HR=4.9, 95% CI 1.6-14.8, p=0.0047), and the risk increased as more of the genome was affected. Conclusions: Genome wide analysis of CNAs provides a common platform for evaluation of chromosome instability for cancer risk assessment as well as identification of common regions of alteration that can be further studied for biomarker discovery.

Item Type: Article
Additional Information: This article is available to subscribers only for the first 12 months following publication.
DOI: 10.1158/1078-0432.CCR-08-2494
PubMed ID: 19417022
NIHMSID: NIHMS103143
PMCID: PMC2684570
Grant Numbers: K07CA089147, PO1CA91955
Keywords or MeSH Headings: Aged; Barrett Esophagus/*genetics/pathology; *Chromosomal Instability; Chromosome Aberrations; Comparative Genomic Hybridization/methods; DNA, Neoplasm/metabolism; Disease Progression; Esophageal Neoplasms/*genetics/pathology; Flow Cytometry; *Gene Dosage; Genetic Predisposition to Disease/genetics; Genome-Wide Association Study; Humans; Loss of Heterozygosity; Middle Aged; Neoplasm Staging
Subjects: Diseases > Solid tumors > Digestive system cancer
Cellular and Organismal Processes > Genetic processes > Genomic instability
Depositing User: Library Staff
Date Deposited: 28 Sep 2009 18:03
Last Modified: 14 Feb 2012 14:42
URI: http://authors.fhcrc.org/id/eprint/227

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