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Integrated Analysis of TP53 Gene and Pathway Alterations in The Cancer Genome Atlas

2019; Cell Press; Volume: 28; Issue: 5 Linguagem: Inglês

10.1016/j.celrep.2019.07.001

2639-1856

Lawrence A. Donehower, Thierry Soussi, Anil Korkut, Yuexin Liu, André Schultz, Maria Cardenas, Xubin Li, Özgün Babur, Teng‐Kuei Hsu, Olivier Lichtarge, John N. Weinstein, Rehan Akbani, David A. Wheeler,

RNA modifications and cancer

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.