Epigenetic gene silencing in cancer initiation and progression

Kenneth Nephew, Tim Hui Ming Huang

Research output: Contribution to journalArticle

135 Citations (Scopus)

Abstract

Hypermethylation of CpG islands, an epigenetic event that is not accompanied by changes in DNA sequence, represents an alternative mechanism to deletions or mutations to inactivate tumor suppressor genes. Recent evidence supports the notion that CpG island hypermethylation, by silencing key cancer-related genes, plays a major causal role in cancer. However, a long-standing issue in the field is the sequence of molecular events leading to epigenetic gene silencing. A new model has been proposed that chromatin remodeling, as a result of histone deacetylation and methylation, is the primary event in abrogating transcriptional initiation; subsequently, CpG island hypermethylation establishes a permanent state of gene silencing. Accumulating evidence indicates that CpG island hypermethylation is an early event in cancer development and, in some cases, may precede the neoplastic process. Because of their heritable nature, hypermethylated CpG islands leave 'molecular footprints' in evolving cancer cells and can be used as molecular markers to reconstruct epigenetic progression during tumorigenesis. Furthermore, hypermethylated CpG islands are proving to be useful for molecular classification of different cancer types.

Original languageEnglish
Pages (from-to)125-133
Number of pages9
JournalCancer Letters
Volume190
Issue number2
DOIs
StatePublished - Feb 20 2003

Fingerprint

CpG Islands
Gene Silencing
Epigenomics
Neoplasms
Neoplastic Processes
Chromatin Assembly and Disassembly
Sequence Deletion
Neoplasm Genes
Tumor Suppressor Genes
Histones
Methylation
Carcinogenesis

Keywords

  • CpG island
  • DNA methylation
  • Epigenetics
  • Microarray
  • Ovarian cancer

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology
  • Oncology

Cite this

Epigenetic gene silencing in cancer initiation and progression. / Nephew, Kenneth; Huang, Tim Hui Ming.

In: Cancer Letters, Vol. 190, No. 2, 20.02.2003, p. 125-133.

Research output: Contribution to journalArticle

Nephew, Kenneth ; Huang, Tim Hui Ming. / Epigenetic gene silencing in cancer initiation and progression. In: Cancer Letters. 2003 ; Vol. 190, No. 2. pp. 125-133.
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