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DNA hypomethylation is prevalent even in low-grade breast cancers

Kesmic Jackson1, Mimi C Yu, Kazuko Arakawa

  • 1Department of Biochemistry, Tulane Cancer Center and Human Genetics Program, Tulane Medical School, New Orleans, Louisiana 70112, USA.

Cancer Biology & Therapy
|November 13, 2004
PubMed

Insights

Cancer-associated DNA hypomethylation, particularly at satellite 2 (Sat2) regions, is a significant marker for breast cancer. This genomic demethylation, including global DNA hypomethylation, appears to be an early event in carcinogenesis.

Area of Science:

  • Genomics
  • Cancer Biology
  • Epigenetics

Background:

  • Cancer is frequently associated with widespread epigenetic alterations, including DNA hypomethylation and hypermethylation.
  • Previous research identified cancer-associated DNA hypomethylation often involves satellite 2 (Sat2) DNA, a major component of juxtacentromeric heterochromatin on chromosome 1.

Purpose of the Study:

  • To compare DNA methylation patterns of Sat2 and centromeric satellite DNA (Satalpha) in breast cancer.
  • To assess the utility of Sat2 and Satalpha hypomethylation as biomarkers for breast cancer.
  • To investigate the relationship between satellite DNA hypomethylation, global DNA hypomethylation, and clinicopathological features of breast cancer.

Main Methods:

  • Analysis of Sat2 and Satalpha DNA methylation, alongside overall genomic methylation, in 41 breast adenocarcinomas, 16 non-neoplastic breast tissues, and normal somatic tissues.
  • Comparison of methylation levels between cancer and non-neoplastic samples.
  • Correlation analysis between hypomethylation and tumor grade, stage, lymph node involvement, and hormone receptor status.

Main Results:

  • Breast cancers exhibited significant hypomethylation at Sat2 compared to non-neoplastic breast tissues and normal tissues.
  • Satalpha DNA was hypomethylated in cancers relative to normal tissues, but not significantly different between cancers and non-neoplastic breast tissues.
  • Sat2 hypomethylation strongly correlated with global DNA hypomethylation in cancers, but not with tumor grade, stage, or other clinical parameters.
  • Extensive hypomethylation was observed even in early-stage (grade-1 or stage-1) carcinomas.

Conclusions:

  • Hypomethylation at Sat2 is a more reliable marker for breast cancer than Satalpha hypomethylation.
  • Genomic demethylation, including juxtacentromeric satellite DNA and global DNA, is a common and potentially early event in breast carcinogenesis.

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