p53 mutational spectra and the role of methylated CpG sequences

Mutat Res. 2000 May 30;450(1-2):155-66. doi: 10.1016/s0027-5107(00)00022-1.


The occurrence of tumor-specific mutational spectra in the p53 mutation database provides indirect evidence that implicates certain exogenous and possibly endogenous mutagenic events in human carcinogenesis. In some cases, the distribution of DNA damage along the p53 gene caused by environmental carcinogens can be correlated with the mutational spectra, i.e. hotspots and types of mutations of certain cancers, most notably for nonmelanoma skin cancers and lung cancers in smokers. This concept has been validated by experiments with sunlight and cigarette smoke components representing the polycyclic aromatic hydrocarbon class of carcinogens. A disproportionally high number of mutations in p53 (and other genes) are found at methylated CpG dinucleotides. These sequences are particularly prone to mutagenesis involving endogenous events as well as modification by exogenous carcinogens.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • 5-Methylcytosine
  • Carcinogens / toxicity
  • CpG Islands*
  • Cytosine / analogs & derivatives
  • Cytosine / metabolism
  • DNA Methylation
  • DNA Repair / genetics
  • DNA, Neoplasm / genetics
  • DNA, Neoplasm / metabolism
  • Genes, p53*
  • Humans
  • Lung Neoplasms / etiology
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Mutation*
  • Skin Neoplasms / etiology
  • Skin Neoplasms / genetics
  • Skin Neoplasms / metabolism
  • Smoking / adverse effects
  • Sunlight / adverse effects


  • Carcinogens
  • DNA, Neoplasm
  • 5-Methylcytosine
  • Cytosine