TP53 Variations in Human Cancers: New Lessons from the IARC TP53 Database and Genomics Data

By Liacine Bouaoun, D. Sonkin, M. Ardin, M. Hollstein, G. Byrnes, Jiri Zavadil, Magali Olivier. 2016

693 citations recorded by the source corpus.

TP53 gene mutations are one of the most frequent somatic events in cancer. The IARC TP53 Database (http://p53.iarc.fr) is a popular resource that compiles occurrence and phenotype data on TP53 germline and somatic variations linked to human cancer. The deluge of data coming from cancer genomic studies generates new data on TP53 variations and attracts a growing number of database users for the interpretation of TP53 variants. Here, we present the current contents and functionalities of the IARC TP53 Database and perform a systematic analysis of TP53 somatic mutation data extracted from this database and from genomic data repositories. This analysis showed that IARC has more TP53 somatic mutation data than genomic repositories (29,000 vs. 4,000). However, the more complete screening achieved by genomic studies highlighted some overlooked facts about TP53 mutations, such as the presence of a significant number of mutations occurring outside the DNA‐binding domain in specific cancer types. We also provide an update on TP53 inherited variants including the ones that should be considered as neutral frequent variations. We thus provide an update of current knowledge on TP53 variations in human cancer as well as inform users on the efficient use of the IARC TP53 Database.

Subfields: Cancer Research, Molecular Biology, Oncology

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Citations in the corpus

CADD: predicting the deleteriousness of variants throughout the human genome (2018, neutral): “Examples include the task of discriminating ClinVar pathogenic (7) versus common human genetic variants (8); correlation with experimentally measured functional effects in regulatory elements (9–12); and gene-wide frequencies of somatic mutations in cancer genes (13).”
Variable population prevalence estimates of germline TP53 variants: a gnomAD-based analysis (2018, background): “We acknowledge that insertions and deletions are described in 10%–15% of all the LFS families reported in IARC (Bouaoun et al., 2016), and microdeletions/duplications may be found in to up to 11% of the families (Smith et al.”
Integrated Analysis of TP53 Gene and Pathway Alterations in The Cancer Genome Atlas (2019, background): “, 1989) and was further catalogued in TP53 mutation databases (Bouaoun et al., 2016; Caron de Fromentel and Soussi, 1992; Hollstein et al., 1991; Leroy et al., 2014).”
Genomic and Molecular Landscape of DNA Damage Repair Deficiency across The Cancer Genome Atlas (2018, neutral): “Cancer-associated TP53 mutations may promote these consequences through simple loss of function, as well as by altering transcription or through dominant-negative, gain-of-function mechanisms (Bouaoun et al., 2016; Kastenhuber and Lowe, 2017; Olivier et al., 2010; Pfister and Prives, 2017; Stracquad”