Epigenetic Changes in DNA Methylation in Breast Cancer

Abstract

CpG island hypermethylation is a frequent epigenetic event in cancer. We have recently developed an array-based method, called differential methylation hybridization (DMH), allowing for a genome-wide screening of CpG island hypermethylation in breast cancer cell lines (Hum. Mol. Genet. 8: 459-4%O, 1999) . In the present study, DMH was applied to screen 28 paired primary breast tumor and normal samples, and to determine whether patterns of specific epigenetic alterations correlate%with pathological parameters in the patients analyzed. Amplicons, representing a pool of methylated CpG DNA derived from these samples, were used as hybridization probes in an array panel containing 1,104 CpG island tags. Close to 9 of these tags exhibited extensive hypermethylation in the majority of breast tumors relative to their normal controls, while others had little or no detectable changes. Pattern analysis in a subset of CpG island tags revealed that CpG island hypermethylation is associated with histological grades of breast tumors. Poorly differentiated tumors appeared to exhibit more hypermethylated CpG islands than their moderately or well-differentiated counterparts (Th-O.041) . This early finding lays the groundwork for population-based DMH study and demonstrates the need to develop a database for examining large-scale methylation data and for associating specific epigenetic signatures with clinical parameters in breast cancer.

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Document Details

Document Type
Technical Report
Publication Date
Sep 01, 2000
Accession Number
ADA387830

Entities

People

  • Tim H. Huang

Organizations

  • University of Missouri

Tags

DTIC Thesaurus Topics

  • Breast Cancer
  • Cancer
  • Carcinoma
  • Cell Line
  • Cell Physiological Processes
  • Cells
  • Chemistry
  • Chromosomes
  • Databases
  • Dna Sequence Analysis
  • Gene Expression
  • Genetics
  • Health Services
  • Molecular Dynamics
  • Neoplasms
  • Peptide Growth Factors
  • Proteins

Fields of Study

  • Biology

Readers

  • Molecular and genetic basis of cancer.

Technology Areas

  • Biotechnology
  • Biotechnology - Cancer Biotech