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Journal of Biomedicine and Biotechnology
Volume 2011 (2011), Article ID 780836, 10 pages
http://dx.doi.org/10.1155/2011/780836
Research Article

Diagnosis and Prognostication of Ductal Adenocarcinomas of the Pancreas Based on Genome-Wide DNA Methylation Profiling by Bacterial Artificial Chromosome Array-Based Methylated CpG Island Amplification

1Pathology Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
2Hepatobiliary and Pancreatic Surgery Division, National Cancer Center Hospital, Tokyo 104-0045, Japan
3Cancer Genomics Project, National Cancer Center Research Institute, Tokyo 104-0045, Japan
4Proteome Bioinformatics Project, National Cancer Center Research Institute, Tokyo 104-0045, Japan
5Department of Molecular Cytogenetics, Medical Research Institute and School of Biomedical Science, Tokyo Medical and Dental University, Tokyo 113-8510, Japan
6Cancer Genome Center, Chiba Cancer Center Research Institute, Chiba 260-8717, Japan

Received 22 July 2010; Accepted 12 November 2010

Academic Editor: Alain Filloux

Copyright © 2011 Masahiro Gotoh et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

To establish diagnostic criteria for ductal adenocarcinomas of the pancreas (PCs), bacterial artificial chromosome (BAC) array-based methylated CpG island amplification was performed using 139 tissue samples. Twelve BAC clones, for which DNA methylation status was able to discriminate cancerous tissue (T) from noncancerous pancreatic tissue in the learning cohort with a specificity of 100%, were identified. Using criteria that combined the 12 BAC clones, T-samples were diagnosed as cancers with 100% sensitivity and specificity in both the learning and validation cohorts. DNA methylation status on 11 of the BAC clones, which was able to discriminate patients showing early relapse from those with no relapse in the learning cohort with 100% specificity, was correlated with the recurrence-free and overall survival rates in the validation cohort and was an independent prognostic factor by multivariate analysis. Genome-wide DNA methylation profiling may provide optimal diagnostic markers and prognostic indicators for patients with PCs.