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


Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
30 07 2019
Historique:
received: 29 11 2018
revised: 09 05 2019
accepted: 27 06 2019
entrez: 1 8 2019
pubmed: 1 8 2019
medline: 20 8 2020
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 31365877
pii: S2211-1247(19)30885-X
doi: 10.1016/j.celrep.2019.07.001
pmc: PMC7546539
mid: NIHMS1633512
pii:
doi:

Substances chimiques

MicroRNAs 0
RNA, Neoplasm 0
TP53 protein, human 0
Tumor Suppressor Protein p53 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

1370-1384.e5

Subventions

Organisme : NCI NIH HHS
ID : U24 CA210950
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA210949
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA199461
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA100420
Pays : United States
Organisme : NHGRI NIH HHS
ID : UM1 HG008898
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016672
Pays : United States

Commentaires et corrections

Type : ErratumIn

Informations de copyright

Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.

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Auteurs

Lawrence A Donehower (LA)

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.

Thierry Soussi (T)

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.

Anil Korkut (A)

Department of Bioinformatics and Computational Biology, Division of Science, M.D. Anderson Cancer Center, Houston, TX 77030, USA.

Yuexin Liu (Y)

Department of Bioinformatics and Computational Biology, Division of Science, M.D. Anderson Cancer Center, Houston, TX 77030, USA.

Andre Schultz (A)

Department of Bioinformatics and Computational Biology, Division of Science, M.D. Anderson Cancer Center, Houston, TX 77030, USA.

Maria Cardenas (M)

Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.

Xubin Li (X)

Department of Bioinformatics and Computational Biology, Division of Science, M.D. Anderson Cancer Center, Houston, TX 77030, USA.

Ozgun Babur (O)

Computational Biology Program, Oregon Health and Science University, Portland, OR 97239, USA.

Teng-Kuei Hsu (TK)

Department of Biochemistry & Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.

Olivier Lichtarge (O)

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.

John N Weinstein (JN)

Department of Bioinformatics and Computational Biology, Division of Science, M.D. Anderson Cancer Center, Houston, TX 77030, USA.

Rehan Akbani (R)

Department of Bioinformatics and Computational Biology, Division of Science, M.D. Anderson Cancer Center, Houston, TX 77030, USA.

David A Wheeler (DA)

Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.

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