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Cell Rep. 2019 Jul 30;28(5):1370-1384.e5. doi: 10.1016/j.celrep.2019.07.001.

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

Author information

1
Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: larryd@bcm.edu.
2
Sorbonne Université, UPMC University Paris 06, 75005 Paris, France; Department of Oncology-Pathology, Cancer Center Karolinska (CCK), Karolinska Institutet, Stockholm, Sweden; INSERM, U1138, Équipe 11, Centre de Recherche des Cordeliers, Paris, France.
3
Department of Bioinformatics and Computational Biology, Division of Science, M.D. Anderson Cancer Center, Houston, TX 77030, USA.
4
Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.
5
Computational Biology Program, Oregon Health and Science University, Portland, OR 97239, USA.
6
Department of Biochemistry & Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
7
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Computational and Integrative Biomedical Research Center, Baylor College of Medicine, Houston, TX 77030, USA.

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.

KEYWORDS:

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

PMID:
31365877
DOI:
10.1016/j.celrep.2019.07.001
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