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

The Cancer Genome Atlas Network

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)1370-1384.e5
JournalCell Reports
Volume28
Issue number5
DOIs
StatePublished - Jul 30 2019

Fingerprint

Atlases
p53 Genes
Tumors
Genes
Genome
Cells
Neoplasms
RNA
Mutation
MicroRNAs
Tumor Suppressor Genes
Amplification
Proteins
cdc Genes
Cell Cycle Proteins
Chromosomal Instability
Second Primary Neoplasms
Sequence Deletion
Genomic Instability
Loss of Heterozygosity

Keywords

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

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

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

In: Cell Reports, Vol. 28, No. 5, 30.07.2019, p. 1370-1384.e5.

Research output: Contribution to journalArticle

The Cancer Genome Atlas Network. / Integrated Analysis of TP53 Gene and Pathway Alterations in The Cancer Genome Atlas. In: Cell Reports. 2019 ; Vol. 28, No. 5. pp. 1370-1384.e5.
@article{96b4c5e7bb70456fba903395520fb4da,
title = "Integrated Analysis of TP53 Gene and Pathway Alterations in The Cancer Genome Atlas",
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.",
keywords = "chromosomal instability, p53, p53 signaling pathway, p53 signature, p53 targets, PanCanAtlas, TCGA, The Cancer Genome Atlas, TP53, TP53 mutation",
author = "{The Cancer Genome Atlas Network} and Donehower, {Lawrence A.} and Thierry Soussi and Anil Korkut and Yuexin Liu and A. Schultz and M. Cardenas and X. Li and Ozgun Babur and Hsu, {Teng Kuei} and Olivier Lichtarge and Weinstein, {John N.} and R. Akbani and Wheeler, {David A.}",
year = "2019",
month = "7",
day = "30",
doi = "10.1016/j.celrep.2019.07.001",
language = "English (US)",
volume = "28",
pages = "1370--1384.e5",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "5",

}

TY - JOUR

T1 - Integrated Analysis of TP53 Gene and Pathway Alterations in The Cancer Genome Atlas

AU - The Cancer Genome Atlas Network

AU - Donehower, Lawrence A.

AU - Soussi, Thierry

AU - Korkut, Anil

AU - Liu, Yuexin

AU - Schultz, A.

AU - Cardenas, M.

AU - Li, X.

AU - Babur, Ozgun

AU - Hsu, Teng Kuei

AU - Lichtarge, Olivier

AU - Weinstein, John N.

AU - Akbani, R.

AU - Wheeler, David A.

PY - 2019/7/30

Y1 - 2019/7/30

N2 - 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.

AB - 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.

KW - chromosomal instability

KW - p53

KW - p53 signaling pathway

KW - p53 signature

KW - p53 targets

KW - PanCanAtlas

KW - TCGA

KW - The Cancer Genome Atlas

KW - TP53

KW - TP53 mutation

UR - http://www.scopus.com/inward/record.url?scp=85069583014&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85069583014&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2019.07.001

DO - 10.1016/j.celrep.2019.07.001

M3 - Article

VL - 28

SP - 1370-1384.e5

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 5

ER -