Epigenetic Changes in DNA methylation in Breast Cancer

Abstract

CpG island hypermethylation is a frequent epigenetic event in breast cancer. We have developed a microarray-based technique, called DMH, for the first time providing a tool that can efficiently scan the tumor genome for methylation alterations. The first part of DMH is the generation of GC-rich tags derived from a human CpG island genomic library, CGI. These tags were then arrayed onto solid supports (e.g., nylon membranes). The second part involves the preparation of amplicons, representing a pool of methylated CpG DNA, from tumor or reference samples. Amplicons are used as probes for CpG island array hybridization. The differences in tumor and reference signal intensities on CpG island arrays tested reflect methylation alterations of corresponding sequences in the tumor DNA. DMH was successfully applied to detect specific methylation profiles in a group of breast cancer cell lines, and hypermethylation of CpG island loci was independently confirmed by Southern-based analysis. Subsequent pattern analysis of the positive loci revealed important mechanisms governing aberrant methylation in these cells.

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Document Details

Document Type
Technical Report
Publication Date
Sep 01, 1999
Accession Number
ADA384184

Entities

People

  • Tim H-M Huang

Organizations

  • University of Missouri

Tags

DTIC Thesaurus Topics

  • Biomedical Research
  • Breast Cancer
  • Cancer
  • Cell Line
  • Cell Physiological Processes
  • Cells
  • Chemical Reactions
  • Chemistry
  • Chromosomes
  • Colon Cancer
  • Dna Microarrays
  • Dna Sequence Analysis
  • Genetic Structures
  • Genetics
  • Molecular Dynamics
  • Neoplasms
  • Polymerase Chain Reaction

Fields of Study

  • Biology

Readers

  • Breast cancer cell signaling and growth regulation.
  • Immunology
  • Molecular Genetics