Integrated genomic analysis of the ubiquitin pathway across cancer types

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Title: Integrated genomic analysis of the ubiquitin pathway across cancer types
Authors: Ge, Z
Leighton, JS
Wang, Y
Peng, X
Chen, Z
Chen, H
Sun, Y
Yao, F
Li, J
Zhang, H
Liu, J
Shriver, CD
Hu, H
Piwnica-Worms, H
Ma, L
Liang, H
Item Type: Journal Article
Abstract: Protein ubiquitination is a dynamic and reversible process of adding single ubiquitin molecules or various ubiquitin chains to target proteins. Here, using multidimensional omic data of 9,125 tumor samples across 33 cancer types from The Cancer Genome Atlas, we perform comprehensive molecular characterization of 929 ubiquitin-related genes and 95 deubiquitinase genes. Among them, we systematically identify top somatic driver candidates, including mutated FBXW7 with cancer-type-specific patterns and amplified MDM2 showing a mutually exclusive pattern with BRAF mutations. Ubiquitin pathway genes tend to be upregulated in cancer mediated by diverse mechanisms. By integrating pan-cancer multiomic data, we identify a group of tumor samples that exhibit worse prognosis. These samples are consistently associated with the upregulation of cell-cycle and DNA repair pathways, characterized by mutated TP53, MYC/TERT amplification, and APC/PTEN deletion. Our analysis highlights the importance of the ubiquitin pathway in cancer development and lays a foundation for developing relevant therapeutic strategies.
Issue Date: 3-Apr-2018
Date of Acceptance: 12-Mar-2018
URI: http://hdl.handle.net/10044/1/71263
DOI: https://doi.org/10.1016/j.celrep.2018.03.047
ISSN: 2211-1247
Publisher: Elsevier
Start Page: 213
End Page: 226
Journal / Book Title: Cell Reports
Volume: 23
Issue: 1
Copyright Statement: © 2018 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Sponsor/Funder: SAIC-F-Frederick, Inc
Leidos Biomedical Research, Inc.
Funder's Grant Number: TCGA Pilot Program
15Y011ST
Keywords: Science & Technology
Life Sciences & Biomedicine
Cell Biology
F-BOX PROTEIN
DEUBIQUITINATING ENZYMES
CYCLIN-E
MDM2
LIGASE
PHOSPHORYLATION
DEGRADATION
PTEN
RECOGNITION
ANTAGONISTS
FBXW7
The Cancer Genome Atlas
biomarker
cancer prognosis
pan-cancer analysis
therapeutic targets
tumor subtype
ubiquitin pathway
Cancer Genome Atlas Research Network
ubiquitin pathway
pan-cancer analysis
The Cancer Genome Atlas
tumor subtype
cancer prognosis
therapeutic targets
biomarker
FBXW7
Publication Status: Published
Open Access location: http://www.cell.com/cell-reports/retrieve/pii/S2211124718303929?_returnURL=https:%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2211124718303929%3Fshowall%3Dtrue
Online Publication Date: 2018-04-05
Appears in Collections:Division of Surgery
Division of Cancer



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