Chromosomal instability and copy number alterations in Barrett's esophagus and esophageal adenocarcinoma - PubMed (original) (raw)
Chromosomal instability and copy number alterations in Barrett's esophagus and esophageal adenocarcinoma
Thomas G Paulson et al. Clin Cancer Res. 2009.
Abstract
Purpose: Chromosomal instability, as assessed by many techniques, including DNA content aneuploidy, loss of heterozygosity, 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 loss of heterozygosity 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 (CNA) 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 Bacterial Artificial Chromosome (BAC) array comparative genomic hybridization to characterize CNAs at different stages of progression ranging from early BE to advanced EA.
Results: CNAs were rare in early stages (less than high-grade dysplasia) but were progressively more frequent and larger in later stages (high-grade dysplasia and EA), including high-level amplifications. The number of CNAs correlated highly with DNA content aneuploidy. Patients whose biopsies contained CNAs involving >70 Mbp were at increased risk of progression to DNA content abnormalities or EA (hazards ratio, 4.9; 95% confidence interval, 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 the evaluation of chromosome instability for cancer risk assessment as well as for the identification of common regions of alteration that can be further studied for biomarker discovery.
Figures
Figure 1a- c. Frequency plots of gains and losses throughout the genome in patients with
Y-axis indicates the percentage of patients having gains (in grey, above 0) or losses (in black, below 0) for each BAC in the array, X-axis indicates position on the chromosome from tip of p-telomere to tip of q-telomere. Dotted vertical lines indicate centromere location. The
Figure 2. Overall number of copy number alterations in diploid and aneuploid samples associate with aneuploidy as measured by flow cytometry
Sample with maximum ploidy, or for diploid patients, with maximum number of BAC alterations for each patient is indicated. Area in the oval encompasses data points from 80 patients.
## References
1. 1. Cook MB, Wild CP, Everett SM, et al. Risk of mortality and cancer incidence in Barrett's esophagus. Cancer Epidemiol Biomarkers Prev. 2007;16:2090–6. - PubMed 2. 1. Pohl H, Welch HG. The role of overdiagnosis and reclassification in the marked increase of esophageal adenocarcinoma incidence. J Natl Cancer Inst. 2005;97:142–6. - PubMed 3. 1. Brown LM, Devesa SS. Epidemiologic trends in esophageal and gastric cancer in the United States. Surg Oncol Clin N Am. 2002;11:235–56. - PubMed 4. 1. Thomas T, Abrams KR, De Caestecker JS, Robinson RJ. Meta analysis: Cancer risk in Barrett's oesophagus. Aliment Pharmacol Ther. 2007;26:1465–77. - PubMed 5. 1. Anderson LA, Murray LJ, Murphy SJ, et al. Mortality in Barrett's oesophagus: results from a population based study. Gut. 2003;52:1081–4. - PMC - PubMed
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