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

TitleIntegrated Analysis of TP53 Gene and Pathway Alterations in The Cancer Genome Atlas.
Publication TypeJournal Article
Year of Publication2019
AuthorsDonehower, LA, Soussi, T, Korkut, A, Liu, Y, Schultz, A, Cardenas, M, Li, X, Babur, O, Hsu, T-K, Lichtarge, O, Weinstein, JN, Akbani, R, Wheeler, DA
JournalCell Rep
Date Published2019 Jul 30
KeywordsDatabases, Nucleic Acid, Gene Expression Regulation, Neoplastic, Humans, Loss of Heterozygosity, MicroRNAs, Neoplasms, RNA, Neoplasm, Tumor Suppressor Protein p53

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.

Alternate JournalCell Rep
PubMed ID31365877
PubMed Central IDPMC7546539
Grant ListU24 CA210950 / CA / NCI NIH HHS / United States
U24 CA210949 / CA / NCI NIH HHS / United States
U24 CA199461 / CA / NCI NIH HHS / United States
R01 CA100420 / CA / NCI NIH HHS / United States
UM1 HG008898 / HG / NHGRI NIH HHS / United States
P30 CA016672 / CA / NCI NIH HHS / United States

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