This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Harada, T. Articles by Sasaki, K. Search for Related Content PubMed PubMed Citation Articles by Harada, T. Articles by Sasaki, K.

Interglandular Cytogenetic Heterogeneity Detected by Comparative Genomic Hybridization in Pancreatic Cancer

Department of Pathology [T. H., K. Sh., N. K., K. Sa.] and First Department of Internal Medicine [T. H., K. O., K. Sh., N. K., S. K.], Yamaguchi University School of Medicine, Yamaguchi 755-8505, Japan

The aim of this study is to explore the mechanisms of intratumoral cytogenetic heterogeneity (ICH) in pancreatic cancer. Using comparative genomic hybridization (CGH) analysis, we investigated interglandular variation in 20 primary invasive ductal adenocarcinomas of the pancreas. Three or four adjacent neoplastic glands were individually microdissected from a tumor specimen. Extracted DNA from each gland was amplified by degenerate oligonucleotide primed-PCR, followed by CGH. In addition, DNA index (DI) was measured by laser scanning cytometry in each case. CGH profiles displayed a wide variety of differences between glands within the same tumor in all cases, i.e., interglandular cytogenetic heterogeneity was distinct in pancreatic cancers. In this study, genetic changes detected in all regions of a tumor were classified as "region-independent" alterations, whereas changes seen in at least one, but not all regions were designated as "region-dependent" alterations, which resulted in ICH. The degree of ICH, which was manifested as the ratio of these two types of alterations, correlated closely with DI (Spearman = 0.842; P = 0.0002). Therefore, DI might be a surrogate marker for ICH. These results suggest that with tumor progression, ICH and DNA aneuploidy result from the successive appearance of region-dependent alterations attributable to chromosomal instability in tumor cells. Our data support a concept of individual cell heterogeneity in pancreatic cancer.

This article has been cited by other articles:

				D.-F. Peng, Y. Kanai, M. Sawada, S. Ushijima, N. Hiraoka, S. Kitazawa, and S. Hirohashi DNA methylation of multiple tumor-related genes in association with overexpression of DNA methyltransferase 1 (DNMT1) during multistage carcinogenesis of the pancreas Carcinogenesis, June 1, 2006; 27(6): 1160 - 1168. [Abstract] [Full Text] [PDF]

				A. F. Hezel, A. C. Kimmelman, B. Z. Stanger, N. Bardeesy, and R. A. DePinho Genetics and biology of pancreatic ductal adenocarcinoma. Genes & Dev., May 15, 2006; 20(10): 1218 - 1249. [Abstract] [Full Text] [PDF]

				N. H. Stoecklein, A. M. Luebke, A. Erbersdobler, W. T. Knoefel, W. Schraut, P. E. Verde, F. Stern, P. Scheunemann, M. Peiper, C. F. Eisenberger, et al. Copy Number of Chromosome 17 but Not HER2 Amplification Predicts Clinical Outcome of Patients With Pancreatic Ductal Adenocarcinoma J. Clin. Oncol., December 1, 2004; 22(23): 4737 - 4745. [Abstract] [Full Text] [PDF]

				Y. Nakahara, T. Shiraishi, H. Okamoto, T. Mineta, T. Oishi, K. Sasaki, and K. Tabuchi Detrended fluctuation analysis of genome-wide copy number profiles of glioblastomas using array-based comparative genomic hybridization Neuro-oncol, October 1, 2004; 6(4): 281 - 289. [Abstract] [PDF]

				Y. Yamamoto, H. Matsuyama, T. Furuya, A. Oga, S. Yoshihiro, M. Okuda, S. Kawauchi, K. Sasaki, and K. Naito Centrosome Hyperamplification Predicts Progression and Tumor Recurrence in Bladder Cancer Clin. Cancer Res., October 1, 2004; 10(19): 6449 - 6455. [Abstract] [Full Text] [PDF]

				T. Ueno, A. Tangoku, S. Yoshino, T. Abe, H. Hayashi, H. Toshimitsu, K. Hashimoto, T. Satoh, A. Oga, T. Furuya, et al. Prediction of Nodal Metastasis by Comparative Genomic Hybridization in Biopsy Specimens from Patients with Superficial Esophageal Squamous Cell Carcinoma Clin. Cancer Res., November 1, 2003; 9(14): 5137 - 5141. [Abstract] [Full Text] [PDF]