title: p53 from basic research to clinical applications.
abstract: Mutations on the TP53 tumor suppressor gene and allele loss on chromosome 17p, where this gene has been located, are among the most frequent alterations yet identified in human malignancies. The p53 protein is highly conserved through evolution and expressed in most normal tissues. Wild-type p53 has been shown to control normal cell proliferation possibly through transcriptional regulation. The wild-type TP53 gene can suppress cell transformation and neoplastic cell growth. In contrast, mutant TP53 has lost the tumor suppressing ability and, in most cases, has gained a transformation promoting ability. Many different TP53 mutations have common conformational and functional consequences on the p53 protein. However, all the TP53 mutants are not necessarily equivalent in terms of biological activity: some mutations confer a strong transforming ability, while others lead to truncated products with probably no biological function. Some mutants may exhibit a dominant behavior over wild-type TP53, others may be recessive. Point mutations of TP53 tend to occur on evolutionary conserved positions. However, the TP53 mutational spectrum differs among cancer types, and this fact may reflect different exogenous mutagens and endogenous factors contributing to human carcinogenesis. In defined types of malignancies, the tumors with TP53 alteration or tumors with allele loss on 17p are associated with more aggressive phenotypes than those without these alterations. For these malignancies, the monitoring of TP53 alteration should now be included in therapeutic trials. Germ line mutations on TP53 may also occur. Individuals with constitutional TP53 mutation have a predisposition to a wide variety of neoplasms. Further characterization of this predisposition will enable the definition of the best follow-up for these at-risk patients.
authors.affiliation: Laboratory of Radiopathology, Institut Curie, Paris, France.
authors.forename: O
authors.initials: O
authors.lastname: Tominaga
authors.forename: R
authors.initials: R
authors.lastname: Hamelin
authors.forename: Y
authors.initials: Y
authors.lastname: Remvikos
authors.forename: R J
authors.initials: RJ
authors.lastname: Salmon
authors.forename: G
authors.initials: G
authors.lastname: Thomas
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic; D016161:Genes, Retinoblastoma; D016158:Genes, p53; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000235:genetics; D011379:Prognosis; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
chemical_list: D016159:Tumor Suppressor Protein p53