Reactivating the expression of methylation silenced genes in human cancer

Adam R. Karpf, David A. Jones

Research output: Contribution to journalReview article

217 Citations (Scopus)

Abstract

DNA methylation alterations are now widely recognized as a contributing factor in human tumorigenesis. A significant number of tumor suppressor genes are transcriptionally silenced by promoter hypermethylation, and recent research implicates alterations in chromatin structure as the mechanistic basis for this repression. The enzymes responsible for catalyzing DNA-cytosine methylation, as well as the proteins involved in interpreting the DNA methylation signal, have now been elucidated. Technological advances, including gene expression microarrays and genome scanning techniques, have allowed the comprehensive measurement of DNA methylation changes in human cancers. An important distinction between DNA methylation (epigenetic) and mutation or deletion (genetic) tumor suppressor gene inactivation is that epigenetic inactivation can be abrogated by small molecules, including DNA methyltransferase and histone deacetylase inhibitors. Further, strategies have been developed that combine treatments with drugs that reactivate silenced gene expression with secondary agents that target the re-expressed genes and/or reconstituted signal transduction pathways. In this review, we will discuss in detail the mechanisms of gene silencing by DNA methylation, the techniques used to decipher the complement of methylation-inactivated genes in human cancers, and current and future strategies for reactivating the expression of methylation-silenced genes.

Original languageEnglish (US)
Pages (from-to)5496-5503
Number of pages8
JournalOncogene
Volume21
Issue number35 REV. ISS. 3
DOIs
StatePublished - Aug 12 2002

Fingerprint

DNA Methylation
Methylation
Genes
Neoplasms
Gene Silencing
Tumor Suppressor Genes
Epigenomics
Gene Expression
Histone Deacetylase Inhibitors
Sequence Deletion
Cytosine
Methyltransferases
Chromatin
Signal Transduction
Carcinogenesis
Genome
DNA
Enzymes
Research
Pharmaceutical Preparations

Keywords

  • 5-aza-2′-deoxycytidine
  • Cancer
  • DNA methylation
  • DNA methyltransferase

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Reactivating the expression of methylation silenced genes in human cancer. / Karpf, Adam R.; Jones, David A.

In: Oncogene, Vol. 21, No. 35 REV. ISS. 3, 12.08.2002, p. 5496-5503.

Research output: Contribution to journalReview article

Karpf, Adam R. ; Jones, David A. / Reactivating the expression of methylation silenced genes in human cancer. In: Oncogene. 2002 ; Vol. 21, No. 35 REV. ISS. 3. pp. 5496-5503.
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