Cited by 884Cancer-related Molecular PathwaysCancer Genomics and DiagnosticsGenetic factors in colorectal cancer

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TP53 mutations in human cancers: functional selection and impact on cancer prognosis and outcomes

Petitjean, A, Achatz, M I W, Borresen-Dale, A L, Hainaut, P, Olivier, M·2007·Oncogene

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Abstract

A large amount of data is available on the functional impact of missense mutations in TP53 and on mutation patterns in many different cancers. New data on mutant p53 protein function, cancer phenotype and prognosis have recently been integrated in the International Agency for Research on Cancer TP53 database (http://www-p53.iarc.fr/). Based on these data, we summarize here current knowledge on the respective roles of mutagenesis and biological selection of mutations with specific functional characteristic in shaping the patterns and phenotypes of mutations observed in human cancers. The main conclusion is that intrinsic mutagenicity rates, loss of transactivation activities, and to a lesser extent, dominant-negative activities are the main driving forces that determine TP53 mutation patterns and influence tumor phenotype. In contrast, current experimental data on the acquisition of oncogenic activities (gain of function) by p53 mutants are too scarce and heterogenous to assess whether this property has an impact on tumor development and outcome. In the case of inherited TP53 mutations causing Li-Fraumeni and related syndromes, the age at onset of some tumor types is in direct relation with the degree of loss of transactivation capacity of missense mutations. Finally, studies on large case series demonstrate that TP53 mutations are independent markers of bad prognosis in breast and several other cancers, and that the exact type and position of the mutation influences disease outcome. Further studies are needed to determine how TP53 haplotypes or loss of alleles interact with mutations to modulate their impact on cancer development and prognosis.

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Authors: Petitjean, A., Achatz, M. I. W., Borresen-Dale, A. L., Hainaut, P., & Olivier, M.
Affiliations: Centre international de recherche sur le cancer (FR)
Corresponding author: Hainaut, P
ORCID: Petitjean, A
Achatz, M I W
Hainaut, P
Olivier, M
Venue: Oncogene
Publisher: Springer Science and Business Media LLC
Published: 2007-04-02
Volume: 26
Issue: 15
Pages: 2157-2165
ISSN: 0950-9232 (ISSN-L)
1476-5594
DOI: 10.1038/sj.onc.1210302
OpenAlex: W2042484101
Cited by: 884
References: 117
Citations by year: 2026: 16 · 2025: 29 · 2024: 29 · 2023: 50 · 2022: 55 · 2021: 52 · 2020: 50 · 2019: 53 · 2018: 60 · 2017: 46 · 2016: 57 · 2015: 52 · 2014: 53 · 2013: 43 · 2012: 48
FWCI: 5.08
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Oncogene (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
Keywords: TP53 mutation, missense mutations, dominant-negative p53, gain-of-function, mutagenesis, tumor phenotype, cancer prognosis, Li-Fraumeni syndrome, loss of heterozygosity, breast cancer
MeSH terms: Genetic Markers, Humans, Mutation, Neoplasms, Polymorphism, Genetic, Prognosis, Biomarkers, Tumor, Tumor Suppressor Protein p53, Mutagenesis, Li-Fraumeni Syndrome

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TP53 mutations in human cancers: functional selection and impact on cancer prognosis and outcomes

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