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Department of Pathology and Anatomical Sciences, Ellis Fischel Cancer Center, University of Missouri School of Medicine, Columbia, Missouri 65203 [P. S. Y., H. S., F. R., S. H. W., C. W. C., T. H-M. H.], and Department of Zoology, Life Science College, National Chung Hsing University, Taiwan, Republic of China [C-M. C.]
It is now clear that aberrant DNA methylation observed in cancer cells is not restricted to a few CpG islands, but affects multiple loci. When this epigenetic event occurs at the 5'-end of the regulatory region of genes, it is frequently associated with transcriptional silencing. To investigate further this widespread event in the tumor genome, we developed a novel microarray containing 7776 short GC-rich tags tethered to glass slide surfaces. This DNA chip was used to study 17 paired tissues of breast tumors and normal controls. Amplicons, representing differential pools of methylated DNA fragments between tumors and normal controls, were cohybridized to the microarray panel. Hypermethylation of multiple CpG island loci was then detected in a two-color fluorescence system. Approximately 1% (on average, 83 loci) of these CpG islands examined were hypermethylated in this patient group. Hierarchical clustering segregated these tumors based on their methylation profiles and identified a group of CpG island loci that corresponds to the hormone-receptor status of breast cancer. This observation was independently confirmed by examining a single locus, the promoter of the human glypican 3 gene, which was predominately hypermethylated in the hormone receptor-negative tumors. Our findings support the notion that hypermethylation of critical CpG island loci influences cancer development and produces distinct epigenetic signatures for particular tumor subtypes.
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S. H. Wei, C.-M. Chen, G. Strathdee, J. Harnsomburana, C.-R. Shyu, F. Rahmatpanah, H. Shi, S.-W. Ng, P. S. Yan, K. P. Nephew, et al. Methylation Microarray Analysis of Late-Stage Ovarian Carcinomas Distinguishes Progression-free Survival in Patients and Identifies Candidate Epigenetic Markers Clin. Cancer Res., July 1, 2002; 8(7): 2246 - 2252. [Abstract] [Full Text] [PDF] |
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D. Soulet and S. Rivest Perspective: How to Make Microarray, Serial Analysis of Gene Expression, and Proteomic Relevant to Day-to-Day Endocrine Problems and Physiological Systems Endocrinology, June 1, 2002; 143(6): 1995 - 2001. [Abstract] [Full Text] [PDF] |
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H. Shi, P. S. Yan, C.-M. Chen, F. Rahmatpanah, C. Lofton-Day, C. W. Caldwell, and T. H.-M. Huang Expressed CpG Island Sequence Tag Microarray for Dual Screening of DNA Hypermethylation and Gene Silencing in Cancer Cells Cancer Res., June 1, 2002; 62(11): 3214 - 3220. [Abstract] [Full Text] [PDF] |
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J. M. Ordway and T. Curran Methylation Matters: Modeling a Manageable Genome Cell Growth Differ., April 1, 2002; 13(4): 149 - 162. [Full Text] [PDF] |
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R. Ohlsson and C. Kanduri New Twists on the Epigenetics of CpG Islands Genome Res., April 1, 2002; 12(4): 525 - 526. [Full Text] [PDF] |
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A. S. Weinmann, P. S. Yan, M. J. Oberley, T. H.-M. Huang, and P. J. Farnham Isolating human transcription factor targets by coupling chromatin immunoprecipitation and CpG island microarray analysis Genes & Dev., January 15, 2002; 16(2): 235 - 244. [Abstract] [Full Text] [PDF] |
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