Abstract
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.
Keywords
BiologyGermlineGermline mutationGeneticsGeneContext (archaeology)Somatic cellMutagenesisCancerMutationLi–Fraumeni syndromeCoding regionHuman geneticsHuman genomeCancer researchGenomeComputational biology
Affiliated Institutions
Related Publications
The landscape of cancer genes and mutational processes in breast cancer
All cancers carry somatic mutations in their genomes. A subset, known as driver mutations, confer clonal selective advantage on cancer cells and are causally implicated in oncog...
A Hypermutation Phenotype and Somatic <i>MSH6</i> Mutations in Recurrent Human Malignant Gliomas after Alkylator Chemotherapy
Abstract Malignant gliomas have a very poor prognosis. The current standard of care for these cancers consists of extended adjuvant treatment with the alkylating agent temozolom...
COSMIC: the Catalogue Of Somatic Mutations In Cancer
This FAIRsharing record describes: The Catalogue of Somatic Mutations in Cancer (COSMIC) is a database of manually-curated somatic mutation information relating to human cancers...
Clonal Hematopoiesis and Blood-Cancer Risk Inferred from Blood DNA Sequence
Clonal hematopoiesis with somatic mutations is readily detected by means of DNA sequencing, is increasingly common as people age, and is associated with increased risks of hemat...
Gene-Expression Profiles in Hereditary Breast Cancer
Significantly different groups of genes are expressed by breast cancers with BRCA1 mutations and breast cancers with BRCA2 mutations. Our results suggest that a heritable mutati...
Publication Info
- Year
- 2009
- Type
- review
- Volume
- 2
- Issue
- 1
- Pages
- a001008-a001008
- Citations
- 2114
- Access
- Closed
External Links
Social Impact
Altmetric
PlumX Metrics
Social media, news, blog, policy document mentions
Citation Metrics
2114
OpenAlex
Cite This
Magali Olivier,
Monica Hollstein,
Pierre Hainaut
(2009).
TP53 Mutations in Human Cancers: Origins, Consequences, and Clinical Use.
Cold Spring Harbor Perspectives in Biology
, 2
(1)
, a001008-a001008.
https://doi.org/10.1101/cshperspect.a001008
Identifiers
- DOI
- 10.1101/cshperspect.a001008