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A pan-cancer analysis of enhancer expression in nearly 9000 patient samples

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Title: A pan-cancer analysis of enhancer expression in nearly 9000 patient samples
Authors: Chen, H
Li, C
Peng, X
Zhou, Z
Weinstein, JN
Liang, H
Item Type: Journal Article
Abstract: The role of enhancers, a key class of non-coding regulatory DNA elements, in cancer development has increasingly been appreciated. Here, we present the detection and characterization of a large number of expressed enhancers in a genome-wide analysis of 8928 tumor samples across 33 cancer types using TCGA RNA-seq data. Compared with matched normal tissues, global enhancer activation was observed in most cancers. Across cancer types, global enhancer activity was positively associated with aneuploidy, but not mutation load, suggesting a hypothesis centered on “chromatin-state” to explain their interplay. Integrating eQTL, mRNA co-expression, and Hi-C data analysis, we developed a computational method to infer causal enhancer-gene interactions, revealing enhancers of clinically actionable genes. Having identified an enhancer ∼140 kb downstream of PD-L1, a major immunotherapy target, we validated it experimentally. This study provides a systematic view of enhancer activity in diverse tumor contexts and suggests the clinical implications of enhancers.
Issue Date: 5-Apr-2018
Date of Acceptance: 13-Mar-2018
URI: http://hdl.handle.net/10044/1/71225
DOI: https://doi.org/10.1016/j.cell.2018.03.027
ISSN: 0092-8674
Publisher: Elsevier
Start Page: 386
End Page: 399.e12
Journal / Book Title: Cell
Volume: 173
Issue: 2
Copyright Statement: © 2018 The Authors. Published by Elsevier Inc. 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
Biochemistry & Molecular Biology
Cell Biology
TRANSCRIPTIONAL ENHANCERS
GENE-EXPRESSION
SUPER-ENHANCERS
CLASS DISCOVERY
GENOME
LANDSCAPE
MAP
IDENTIFICATION
ORGANIZATION
PRINCIPLES
PD-L1 expression
The Cancer Genome Atlas
aneuploidy
chromatin state
enhancer expression
mutation burden
pan-cancer analysis
prognostic markers
Aneuploidy
B7-H1 Antigen
Chromatin
Databases, Genetic
Enhancer Elements, Genetic
Gene Expression Regulation, Neoplastic
Humans
Immunotherapy
Neoplasms
Sequence Analysis, RNA
Survival Rate
Cancer Genome Atlas Research Network
Chromatin
Humans
Neoplasms
Aneuploidy
Immunotherapy
Survival Rate
Sequence Analysis, RNA
Gene Expression Regulation, Neoplastic
Databases, Genetic
Enhancer Elements, Genetic
B7-H1 Antigen
Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Cell Biology
TRANSCRIPTIONAL ENHANCERS
GENE-EXPRESSION
SUPER-ENHANCERS
CLASS DISCOVERY
GENOME
LANDSCAPE
MAP
IDENTIFICATION
ORGANIZATION
PRINCIPLES
06 Biological Sciences
11 Medical and Health Sciences
Developmental Biology
Publication Status: Published
Open Access location: https://www.cell.com/cell/fulltext/S0092-8674(18)30307-6?_returnURL=https:%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867418303076%3Fshowall%3Dtrue
Online Publication Date: 2018-04-05
Appears in Collections:Department of Surgery and Cancer