Chapter category: Oncogenes

TP53 Mutations in Human Cancers: Selection versus Mutagenesis and Pierre Hainaut

This chapter appears in the following book:

p53

Edited by: Theodore Hupp and Ayeda Ayed
ISBN: TBA
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Chapter authors:
Magali Olivier, Stephanie Courtois, Claude Caron de Fromentel and Pierre Hainaut

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TP53 differs from most other cancer-related genes by the very high prevalence of missense mutations which result in the expression of a mutant protein. Considerable variations are observed between mutation patterns from different types of cancer and from different population groups, reflecting both mutagenesis and selection processes. These mutations are compiled in a database which includes information on tumor histology and patient’s characteristics, allowing analyzes of TP53 mutation patterns according to various parameters (http://www.iarc.fr/p53). TP53 mutations are also observed in the germline and are associated with a syndrome of early onset cancers, the Li-Fraumeni syndrome. Germline and somatic mutations are very similar and affect codons located in the DNA-binding domain of the protein. Six major hotspot codons account for 30% of all mutations. Most mutations lead to proteins with impaired transactivation activities. However, all mutations are not equivalent. In addition to the loss of wild-type activity, some mutants exert dominant-negative effects and/ or acquire new pro-oncogenic activities. Our understanding of the behavior of mutant p53 is far from complete, but holds promises for applications to cancer risk assessment, early diagnosis, prediction of disease outcome, as well as for development of new therapeutic strategies.

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Chapter category: Oncogenes

TP53 Mutations in Human Cancers: Selection versus Mutagenesis and Pierre Hainaut

Additional chapters from this book:

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