Abstract
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. Donehower et al. performed a comprehensive analysis of the effects of TP53 gene mutation in 32 cancer types and 10,225 patients from The Cancer Genome Atlas (TCGA). Data synthesized from five different analysis platforms show how mutant TP53 increases genomic instability and induces major pathway signaling changes in cancer cells.
Original language | English (US) |
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Pages (from-to) | 1370-1384.e5 |
Journal | Cell Reports |
Volume | 28 |
Issue number | 5 |
DOIs | |
State | Published - Jul 30 2019 |
Keywords
- PanCanAtlas
- TCGA
- TP53
- TP53 mutation
- The Cancer Genome Atlas
- chromosomal instability
- p53
- p53 signaling pathway
- p53 signature
- p53 targets
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology