The TP53 website: an integrative resource centre for the TP53 mutation database and TP53 mutant analysis

Abstract

A novel resource centre for TP53 mutations and mutants has been developed (http://p53.fr). TP53 gene dysfunction can be found in the majority of human cancer types. The potential use of TP53 mutation as a biomarker for clinical studies or exposome analysis has led to the publication of thousands of reports describing the TP53 gene status in >10,000 tumours. The UMD TP53 mutation database was created in 1990 and has been regularly updated. The 2012 release of the database has been carefully curated, and all suspicious reports have been eliminated. It is available either as a flat file that can be easily manipulated or as novel multi-platform analytical software that has been designed to analyse various aspects of TP53 mutations. Several tools to ascertain TP53 mutations are also available for download. We have developed TP53MULTLoad, a manually curated database providing comprehensive details on the properties of 2549 missense TP53 mutants. More than 100,000 entries have been arranged in 39 different activity fields, such as change of transactivation on various promoters, apoptosis or growth arrest. For several hot spot mutants, multiple gain of function activities are also included. The database can be easily browsed via a graphical user interface.

Figure 1.

Trends in TP53 mutation publications. (A) Number of mutations published each year using either Sanger methodology (Red) or NGS (blue). For 2012 (last column on the left), only the first 6 months of the year were taken into account. Only publications describing molecular analysis of TP53 mutations were included in this analysis. (B) Number of novel TP53 mutants described each year since the first discovery.

Figure 2.

Summary of the content of the latest version of the TP53 mutation database. Mutants and mutations have been classified into three categories (missense, frameshift and nonsense). The features of the 15 most frequent mutations in the database are shown in the right part of the figure.

Figure 3.

An overview of the various features of TP53_DBM_INVEST. (A) Distribution of mutational events; (B) List and description of hot spot mutations; (C) Distribution of tandem mutations; (D) Frequency of TP53 mutations in various regions of the TP53 gene; (E) Summary of the strategy used for the analysis of TP53 mutations (top panel: number of studies focusing on sequencing of different TP53 gene regions; bottom panel: number of studies adopting specific experimental approaches); (F) Frequency of TP53 mutations at dipyrimidine sites for specific cancer types; (G) Overall distribution of TP53 mutations in the protein.

Figure 4.

Biological activity report for the hotspot mutant R175H. (A) Downloadable table view listing results from different assays, systems and experimental approaches. (B) Graphical summary of DNA binding and transactivation results. (C) Example of the hyperlink to the publications curated in this section of the database.