TP53 mutations in human cancers: origins, consequences, and clinical use.
Somatic mutations in the TP53 gene are one of the most frequent alterations in human cancers, and germline mutations are the underlying cause of Li-Fraumeni syndrome, which predisposes to a wide spectrum of early-onset cancers. Most mutations are single-base substitutions distributed throughout the coding sequence. Their diverse types and positions may inform on the nature of mutagenic mechanisms involved in cancer etiology. TP53 mutations are also potential prognostic and predictive markers, as well as targets for pharmacological intervention. All mutations found in human cancers are compiled in the IARC TP53 Database (http://www-p53.iarc.fr/). A human TP53 knockin mouse model (Hupki mouse) provides an experimental model to study mutagenesis in the context of a human TP53 sequence. Here, we summarize current knowledge on TP53 gene variations observed in human cancers and populations, and current clinical applications derived from this knowledge.
Olivier
Magali
M
Group of Molecular Carcinogenesis, International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372 Lyon Cedex 08, France.
Hollstein
Monica
M
Hainaut
Pierre
P
D000818:Animals; D002273:Carcinogens; D018899:CpG Islands; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D016296:Mutagenesis; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*; D011379:Prognosis
D002273:Carcinogens