Spontaneous and inherited TP53 genetic alterations

• Published in: Oncogene Vol. 40; no. 41; pp. 5975 - 5983
• Main Author: Levine, Arnold J.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 14.10.2021; Nature Publishing Group
• Subjects: 631/208/68; 631/67/68; Animals; Apoptosis; Cancer; Cell Biology; Development and progression; Environmental factors; Epigenetic inheritance; Epigenetics; Gene mutations; Gene polymorphism; Genetic aspects; Human Genetics; Humans; Internal Medicine; Medicine; Medicine & Public Health; Missense mutation; Mutation; Neoplasms - genetics; Neoplasms - therapy; Oncology; Oncology, Experimental; p53 Protein; Phenotypes; Review; Review Article; Sequence Analysis, Protein - methods; Tumor proteins; Tumor Suppressor Protein p53 - genetics; Tumors; United States
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/s41388-021-01991-3

The p53 protein is a transcription factor that prevents tumors from developing. In spontaneous and inherited cancers there are many different missense mutations in the DNA binding domain of the TP53 gene that contributes to tumor formation. These mutations produce a wide distribution in the transcriptional capabilities of the mutant p53 proteins with over four logs differences in the efficiencies of forming cancers in many diverse tissue types. These inherited and spontaneous TP53 mutations produce proteins that interact with both genetic and epigenetic cellular modifiers of p53 function and their inherited polymorphisms to produce a large number of diverse phenotypes in individual patients. This manuscript reviews these variables and discusses how the combinations of TP53 genetic alterations interact with genetic polymorphisms, epigenetic alterations, and environmental factors to begin predicting and modifying patient outcomes and provide a better understanding for new therapeutic opportunities.