© 1999 by Oxford University Press
Journal of the National Cancer Institute, Vol. 91, No. 24, 2087-2095,
December 15, 1999
© 1999 Oxford University Press
Clonal Expansion and Loss of Heterozygosity at Chromosomes 9p and 17p in Premalignant Esophageal (Barrett's) Tissue
Affiliations of authors: P. C. Galipeau, L. J. Prevo, C. A. Sanchez (Programs in Cancer Biology and Gastrointestinal Oncology, Divisions of Human Biology and Public Health Sciences), G. M. Longton (Department of Biostatistics, Division of Public Health Sciences), Fred Hutchinson Cancer Research Center, Seattle, WA; B. J. Reid, Programs in Cancer Biology and Gastrointestinal Oncology, Divisions of Human Biology and Public Health Sciences, Fred Hutchinson Cancer Research Center, and Departments of Medicine and Genetics, University of Washington, Seattle.
Correspondence to: Brian J. Reid, M.D., Ph.D., C1-015 Fred Hutchinson Cancer Research Center, Seattle, WA 98109 (e-mail: pgal{at}fhcrc.org).
BACKGROUND: Abnormalities involving the p16 (also known as cyclin-dependent kinase N2 [CDKN2], p16 [INK4a], or MTS1) and p53 (also known as TP53) tumor suppressor genes are highly prevalent in esophageal adenocarcinomas. Loss of heterozygosity (LOH) at 9p21 and 17p13 chromosomes (locations for p16 and p53 genes, respectively) is frequently observed in the premalignant condition, Barrett's esophagus. We studied extensively the distribution and heterogeneity of LOH at 9p and 17p chromosomes throughout the Barrett's segment in patients who have not yet developed esophageal adenocarcinoma. METHODS: We evaluated 404 samples from 61 consecutive patients enrolled in the Seattle Barrett's Esophagus Study from February 1995 through September 1998. All patients had high-grade dysplasia but no diagnosis of cancer. The samples were assayed for LOH at 9p and 17p chromosomes after amplification of genomic DNA by use of polymerase chain reaction and DNA genotyping. The cell fractions were purified by flow cytometry on the basis of DNA content and proliferation-associated antigen labeling. Association between LOH at 9p and LOH at 17p with flow cytometric abnormalities was determined by chi-squared test, and logistic regression models were used to model and test for the extent to which a particular genotype was found in 2-cm intervals. RESULTS and CONCLUSIONS: LOH at 9p and 17p chromosomes are highly prevalent somatic genetic lesions in premalignant Barrett's tissue. LOH at 9p is more common than LOH at 17p in diploid samples and can be detected over greater regions of Barrett's epithelium. In most patients with high-grade dysplasia, the Barrett's mucosa contains a mosaic of clones and subclones with different patterns of LOH. Some clones had expanded to involve extensive regions of Barrett's epithelium. LOH at 9p and 17p chromosomes may be useful biomarkers to stratify patients' risk of progression to esophageal cancer.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. Xing, J. A. Ajani, M. Chen, J. Izzo, J. Lin, Z. Chen, J. Gu, and X. Wu Constitutive Short Telomere Length of Chromosome 17p and 12q but not 11q and 2p Is Associated with an Increased Risk for Esophageal Cancer Cancer Prevention Research, May 1, 2009; 2(5): 459 - 465. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. L. Chao, C. A. Sanchez, P. C. Galipeau, P. L. Blount, T. G. Paulson, D. S. Cowan, K. Ayub, R. D. Odze, P. S. Rabinovitch, and B. J. Reid Cell Proliferation, Cell Cycle Abnormalities, and Cancer Outcome in Patients with Barrett's Esophagus: A Long-term Prospective Study Clin. Cancer Res., November 1, 2008; 14(21): 6988 - 6995. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. L. Chao, J. T. Eck, D. E. Brash, C. C. Maley, and E. G. Luebeck Preneoplastic lesion growth driven by the death of adjacent normal stem cells PNAS, September 30, 2008; 105(39): 15034 - 15039. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S J Leedham, S L Preston, S A C McDonald, G Elia, P Bhandari, D Poller, R Harrison, M R Novelli, J A Jankowski, and N A Wright Individual crypt genetic heterogeneity and the origin of metaplastic glandular epithelium in human Barrett's oesophagus Gut, August 1, 2008; 57(8): 1041 - 1048. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Nancarrow, H. Y. Handoko, B. M. Smithers, D. C. Gotley, P. A. Drew, D. I. Watson, A. D. Clouston, N. K. Hayward, D. C. Whiteman, and for the Australian Cancer Study and the Study of D Genome-Wide Copy Number Analysis in Esophageal Adenocarcinoma Using High-Density Single-Nucleotide Polymorphism Arrays Cancer Res., June 1, 2008; 68(11): 4163 - 4172. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Dvorak, C. M Payne, M. Chavarria, L. Ramsey, B. Dvorakova, H. Bernstein, H. Holubec, R. E Sampliner, N. Guy, A. Condon, et al. Bile acids in combination with low pH induce oxidative stress and oxidative DNA damage: relevance to the pathogenesis of Barrett's oesophagus Gut, June 1, 2007; 56(6): 763 - 771. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. L. Chao, C. C. Maley, X. Wu, D. C. Farrow, P. C. Galipeau, C. A. Sanchez, T. G. Paulson, P. S. Rabinovitch, B. J. Reid, M. R. Spitz, et al. Mutagen Sensitivity and Neoplastic Progression in Patients with Barrett's Esophagus: A Prospective Analysis. Cancer Epidemiol. Biomarkers Prev., October 1, 2006; 15(10): 1935 - 1940. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. J. Wongsurawat, J. C. Finley, P. C. Galipeau, C. A. Sanchez, C. C. Maley, X. Li, P. L. Blount, R. D. Odze, P. S. Rabinovitch, and B. J. Reid Genetic Mechanisms of TP53 Loss of Heterozygosity in Barrett's Esophagus: Implications for Biomarker Validation. Cancer Epidemiol. Biomarkers Prev., March 1, 2006; 15(3): 509 - 516. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Britt-Compton, J. Rowson, M. Locke, I. Mackenzie, D. Kipling, and D. M. Baird Structural stability and chromosome-specific telomere length is governed by cis-acting determinants in humans Hum. Mol. Genet., March 1, 2006; 15(5): 725 - 733. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. F. Souza and S. J. Spechler Concepts in the Prevention of Adenocarcinoma of the Distal Esophagus and Proximal Stomach CA Cancer J Clin, November 1, 2005; 55(6): 334 - 351. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. C. Maley, P. C. Galipeau, X. Li, C. A. Sanchez, T. G. Paulson, P. L. Blount, and B. J. Reid The Combination of Genetic Instability and Clonal Expansion Predicts Progression to Esophageal Adenocarcinoma Cancer Res., October 15, 2004; 64(20): 7629 - 7633. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. C. Maley, P. C. Galipeau, X. Li, C. A. Sanchez, T. G. Paulson, and B. J. Reid Selectively Advantageous Mutations and Hitchhikers in Neoplasms: p16 Lesions Are Selected in Barrett's Esophagus Cancer Res., May 15, 2004; 64(10): 3414 - 3427. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. K. Meeker, J. L. Hicks, C. A. Iacobuzio-Donahue, E. A. Montgomery, W. H. Westra, T. Y. Chan, B. M. Ronnett, and A. M. De Marzo Telomere Length Abnormalities Occur Early in the Initiation of Epithelial Carcinogenesis Clin. Cancer Res., May 15, 2004; 10(10): 3317 - 3326. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. T. Barrett, D. Pritchard, C. Palanca-Wessels, J. Anderson, B. J. Reid, and P. S. Rabinovitch Molecular Phenotype of Spontaneously Arising 4N (G2-Tetraploid) Intermediates of Neoplastic Progression in Barrett's Esophagus Cancer Res., July 15, 2003; 63(14): 4211 - 4217. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. E. Rudolph, T. L. Vaughan, A. R. Kristal, P. L. Blount, D. S. Levine, P. C. Galipeau, L. J. Prevo, C. A. Sanchez, P. S. Rabinovitch, and B. J. Reid Serum Selenium Levels in Relation to Markers of Neoplastic Progression Among Persons With Barrett's Esophagus J Natl Cancer Inst, May 21, 2003; 95(10): 750 - 757. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Pozo-Garcia, S. J. Diaz-Cano, B. Taback, and D. S.B. Hoon Clonal Origin and Expansions in Neoplasms: Biologic and Technical Aspects Must Be Considered Together Am. J. Pathol., January 1, 2003; 162(1): 353 - 355. [Full Text] [PDF]
|
|
|
|
|
|
T. L. Vaughan, A. R. Kristal, P. L. Blount, D. S. Levine, P. C. Galipeau, L. J. Prevo, C. A. Sanchez, P. S. Rabinovitch, and B. J. Reid Nonsteroidal Anti-inflammatory Drug Use, Body Mass Index, and Anthropometry in Relation to Genetic and Flow Cytometric Abnormalities in Barrett's Esophagus Cancer Epidemiol. Biomarkers Prev., August 1, 2002; 11(8): 745 - 752. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. O'Shaughnessy, G. J. Kelloff, G. B. Gordon, A. J. Dannenberg, W. K. Hong, C. J. Fabian, C. C. Sigman, M. M. Bertagnolli, S. P. Stratton, S. Lam, et al. Treatment and Prevention of Intraepithelial Neoplasia: An Important Target for Accelerated New Agent Development : Recommendations of the American Association for Cancer Research Task Force on the Treatment and Prevention of Intraepithelial Neoplasia Clin. Cancer Res., February 1, 2002; 8(2): 314 - 346. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Wong, T. G. Paulson, L. J. Prevo, P. C. Galipeau, G. Longton, P. L. Blount, and B. J. Reid p16INK4a Lesions Are Common, Early Abnormalities that Undergo Clonal Expansion in Barrett's Metaplastic Epithelium Cancer Res., November 1, 2001; 61(22): 8284 - 8289. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. P. Tabor, R. H. Brakenhoff, V. M. M. van Houten, J. A. Kummer, M. H. J. Snel, P. J. F. Snijders, G. B. Snow, C. R. Leemans, and B. J. M. Braakhuis Persistence of Genetically Altered Fields in Head and Neck Cancer Patients: Biological and Clinical Implications Clin. Cancer Res., June 1, 2001; 7(6): 1523 - 1532. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Potter Morphostats: A Missing Concept in Cancer Biology Cancer Epidemiol. Biomarkers Prev., March 1, 2001; 10(3): 161 - 170. [Abstract] [Full Text]
|
|
|
|
|
|
I.-M. Shih, W. Zhou, S. N. Goodman, C. Lengauer, K. W. Kinzler, and B. Vogelstein Evidence That Genetic Instability Occurs at an Early Stage of Colorectal Tumorigenesis Cancer Res., February 1, 2001; 61(3): 818 - 822. [Abstract] [Full Text]
|
|
|
|
|
|
A. A.G. van Tilborg, A. de Vries, M. de Bont, L. E. Groenfeld, T. H. van der Kwast, and E. C. Zwarthoff Molecular evolution of multiple recurrent cancers of the bladder Hum. Mol. Genet., December 1, 2000; 9(20): 2973 - 2980. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R. Dunn, J. Garde, K. Dolan, J. R. Gosney, B. C. Oates, A. J. M. Watson, P. Fielding, and J. K. Field The Evolution of Loss of Heterozygosity on Chromosome 17 during the Progression to Barrett's Adenocarcinoma Involves a Unique Combination of Target Sites in Individual Specimens Clin. Cancer Res., October 1, 2000; 6(10): 4033 - 4042. [Abstract] [Full Text]
|
|
|
|
|
|
A. Walch, J. Mueller, H. Hofler, and M. Werner Re: Clonal Expansion and Loss of Heterozygosity at Chromosomes 9p and 17p in Premalignant Esophageal (Barrett's) Tissue J Natl Cancer Inst, July 19, 2000; 92(14): 1182 - 1182. [Full Text] [PDF]
|
|