Journal article
Methylation Profiling of CpG Islands in Human Breast Cancer Cells
Human molecular genetics, Vol.8(3), pp.459-470
03/1999
DOI: 10.1093/hmg/8.3.459
PMID: 9949205
Abstract
CpG island hypermethylation is known to be associated with gene silencing in cancer. This epigenetic event is generally accepted as a stochastic process in tumor cells resulting from aberrant DNA methyltransferase (DNA-MTase) activities. Specific patterns of CpG island methylation could result from clonal selection of cells having growth advantages due to silencing of associated tumor suppressor genes. Alternatively, methylation patterns may be determined by other, as yet unidentified factors. To explore further the underlying mechanisms, we developed a novel array-based method, called differential methylation hybridization (DMH), which allows a genome-wide screening of hypermethylated CpG islands in tumor cells. DMH was used to determine the methylation status of <276 CpG island loci in a group of breast cancer cell lines. Between 5 and 14% of these loci were hypermethylated extensively in these cells relative to a normal control. Pattern analysis of 30 positive loci by Southern hybridization indicated that CpG islands might differ in their susceptibility to hypermethylation. Loci exhibiting preexisting methylation in normal controls were more susceptible to de novo methylation in these cancer cells than loci without this condition. In addition, these cell lines exhibited different intrinsic abilities to methylate CpG islands not directly associated with methyl-transferase activities. Our study provides evidence that, aside from random DNA-MTase action, additional cellular factors exist that govern aberrant methylation in breast cancer cells.
Details
- Title: Subtitle
- Methylation Profiling of CpG Islands in Human Breast Cancer Cells
- Creators
- Tim Hui-Ming Huang - Departments of Pathology and Anatomical Sciences, Ellis Fischel Cancer Center, University of Missouri, 115 Business Loop I-70 West, Columbia, MO 65203, USAMartin R Perry - Departments of Pathology and Anatomical Sciences, Ellis Fischel Cancer Center, University of Missouri, 115 Business Loop I-70 West, Columbia, MO 65203, USADouglas E Laux - Departments of Pathology and Anatomical Sciences, Ellis Fischel Cancer Center, University of Missouri, 115 Business Loop I-70 West, Columbia, MO 65203, USA
- Resource Type
- Journal article
- Publication Details
- Human molecular genetics, Vol.8(3), pp.459-470
- Publisher
- Oxford University Press
- DOI
- 10.1093/hmg/8.3.459
- PMID
- 9949205
- ISSN
- 0964-6906
- eISSN
- 1460-2083
- Language
- English
- Date published
- 03/1999
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984094642802771
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