Beyond the genetic lesions: Gene inactivation by promoter hypermethylation in human cancer

Manel Esteller, Stephen B Baylin, James G. Herman

Research output: Contribution to journalArticle

Abstract

Genetic alterations in key genes are distinctive of a cancer cell. But the tumors also undergo other changes specific of the malignant transformation that do not affect the sequence of DNA. These are given the term epigenetic lesions, and the main one is aberrant methylation. In this review we focus in how promoter hypermethylation silences the expression of genes contributing to the neoplastic phenotype. Well recognized tumor suppressor genes such as p16/INK4a, BRCA1, Rb and V H L became hypermethylated in sporadic tumors with very selective patterns. Other genes recently characterized such as p14/ARF, LKB1, p73, E-cadherin and DAP-Kinase are also epigenetically inactivated in tumors. Furthermore, the methylation mediated silencing of DNA repair and detoxifier genes, such as the mismatch repair gene h MLH1, the alkylrepair MGMT and the carcinogen-protector GSTP1, may cause important genomic damage and mutations. All this recent data may provide a new avenue in how we understand the development, diagnosis and treatment of cancer.

Original languageEnglish (US)
Pages (from-to)61-66
Number of pages6
JournalClinical and Translational Oncology
Volume2
Issue number2
StatePublished - Mar 2000

Fingerprint

Gene Silencing
Neoplasms
Methylation
Genes
Death-Associated Protein Kinases
Tumor Suppressor Protein p14ARF
DNA Mismatch Repair
Cadherins
Tumor Suppressor Genes
Epigenomics
DNA Repair
Carcinogens
Phenotype
Gene Expression
Mutation

Keywords

  • DNA repair genes
  • Epigenetic
  • Human cancer
  • Methylation
  • Promoter
  • Tumor suppressor Genes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Beyond the genetic lesions : Gene inactivation by promoter hypermethylation in human cancer. / Esteller, Manel; Baylin, Stephen B; Herman, James G.

In: Clinical and Translational Oncology, Vol. 2, No. 2, 03.2000, p. 61-66.

Research output: Contribution to journalArticle

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