Integrated Genomic Analysis of the Ubiquitin Pathway across Cancer Types

File(s)

1-s2.0-S2211124718303929-main.pdf (4.9 MB)

Published version

Show more

OA Location

http://www.cell.com/cell-reports/retrieve/pii/S2211124718303929?_returnURL=https:%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2211124718303929%3Fshowall%3Dtrue

Author(s)

Ge, Zhongqi

Leighton, Jake S

Wang, Yumeng

Peng, Xinxin

Chen, Zhongyuan

more

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.

Show more

Date Issued

2018-04-03

Date Acceptance

2018-03-12

Citation

Cell Reports, 2018, 23 (1), pp.213-226

URI

http://hdl.handle.net/10044/1/71263

DOI

https://www.dx.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

SAIC-F-Frederick, Inc

Leidos Biomedical Research, Inc.

Identifier

http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000429092900019&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202

Grant Number

TCGA Pilot Program

15Y011ST

Subjects

ubiquitin pathway

pan-cancer analysis

The Cancer Genome Atlas

tumor subtype

cancer prognosis

therapeutic targets

biomarker

FBXW7

Publication Status

Published

Date Publish Online

2018-04-05