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...

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Bibliographic Details
Published in:Cold Spring Harbor perspectives in biology 2010-01, Vol.2 (1), p.a001008-a001008
Main Authors: Olivier, Magali, Hollstein, Monica, Hainaut, Pierre
Format: Article
Language:English
Subjects:
Animals
Carcinogens
CpG Islands
Gene Expression Regulation, Neoplastic
Genes, p53
Humans
Mice
Mice, Transgenic
Models, Biological
Mutagenesis
Mutation
Neoplasms - genetics
Prognosis
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Summary: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.
ISSN:1943-0264
1943-0264
DOI:10.1101/cshperspect.a001008