Cell Reports
Volume 28, Issue 5, 30 July 2019, Pages 1370-1384.e5
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Integrated Analysis of TP53 Gene and Pathway Alterations in The Cancer Genome Atlas

https://doi.org/10.1016/j.celrep.2019.07.001Get rights and content
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Highlights

  • TP53 mutation effects analyzed by five data platforms in 32 cancers/10,225 patients

  • More than 91% of cancers with TP53 mutations show loss of both functional TP53 alleles

  • TP53 mutation affects genomic stability, global RNA, miRNA, and protein expression

  • Mutant p53 RNA expression signature helps prognostic predictions in 11 cancer types

Summary

The TP53 tumor suppressor gene is frequently mutated in human cancers. An analysis of five data platforms in 10,225 patient samples from 32 cancers reported by The Cancer Genome Atlas (TCGA) enables comprehensive assessment of p53 pathway involvement in these cancers. More than 91% of TP53-mutant cancers exhibit second allele loss by mutation, chromosomal deletion, or copy-neutral loss of heterozygosity. TP53 mutations are associated with enhanced chromosomal instability, including increased amplification of oncogenes and deep deletion of tumor suppressor genes. Tumors with TP53 mutations differ from their non-mutated counterparts in RNA, miRNA, and protein expression patterns, with mutant TP53 tumors displaying enhanced expression of cell cycle progression genes and proteins. A mutant TP53 RNA expression signature shows significant correlation with reduced survival in 11 cancer types. Thus, TP53 mutation has profound effects on tumor cell genomic structure, expression, and clinical outlook.

Keywords

TP53
TP53 mutation
p53
TCGA
The Cancer Genome Atlas
PanCanAtlas
p53 signaling pathway
chromosomal instability
p53 signature
p53 targets

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