A Pan-Cancer Analysis of Enhancer Expression in Nearly 9000 Patient Samples

Han Chen; Chunyan Li; Xinxin Peng; Zhicheng Zhou; John N Weinstein; Han Liang

doi:10.1016/j.cell.2018.03.027

Back

A Pan-Cancer Analysis of Enhancer Expression in Nearly 9000 Patient Samples

Journal article

Open access

Peer reviewed

A Pan-Cancer Analysis of Enhancer Expression in Nearly 9000 Patient Samples

Han Chen, Chunyan Li, Xinxin Peng, Zhicheng Zhou, John N Weinstein and Han Liang

Cell, Vol.173(2), pp.386-399.e12

04/05/2018

DOI: 10.1016/j.cell.2018.03.027

PMCID: PMC5890960

PMID: 29625054

Files and links (1)

url

https://doi.org/10.1016/j.cell.2018.03.027View

Published (Version of record) Open Access

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.

Immunotherapy

Aneuploidy

B7-H1 Antigen - genetics

Chromatin - genetics

Chromatin - metabolism

Databases, Genetic

Enhancer Elements, Genetic - genetics

Gene Expression Regulation, Neoplastic

Humans

Neoplasms - genetics

Neoplasms - mortality

Neoplasms - pathology

Neoplasms - therapy

Sequence Analysis, RNA

Survival Rate

Details

Title: Subtitle: A Pan-Cancer Analysis of Enhancer Expression in Nearly 9000 Patient Samples
Creators: Han Chen - The University of Texas MD Anderson Cancer Center
Chunyan Li - The University of Texas MD Anderson Cancer Center
Xinxin Peng - The University of Texas MD Anderson Cancer Center
Zhicheng Zhou - The University of Texas MD Anderson Cancer Center
John N Weinstein - The University of Texas MD Anderson Cancer Center
Han Liang - The University of Texas MD Anderson Cancer Center
Contributors: Cancer Genome Atlas Network
Deqin Ma - University of Iowa, Pathology
Mohammed M Milhem - University of Iowa, Internal Medicine
Aaron D Bossler - University of Iowa, Pathology
Resource Type: Journal article
Publication Details: Cell, Vol.173(2), pp.386-399.e12
DOI: 10.1016/j.cell.2018.03.027
PMID: 29625054
PMCID: PMC5890960
ISSN: 0092-8674
eISSN: 1097-4172
Grant note: P30 CA016672 / NCI NIH HHS T15 LM007093 / NLM NIH HHS R50 CA221675 / NCI NIH HHS U24 CA210950 / NCI NIH HHS U24 CA210990 / NCI NIH HHS U24 CA210949 / NCI NIH HHS R01 CA175486 / NCI NIH HHS U24 CA210957 / NCI NIH HHS U24 CA209851 / NCI NIH HHS
Language: English
Date published: 04/05/2018
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Pathology; Internal Medicine
Record Identifier: 9984185172502771

Metrics

26 Record Views

216 Times Cited - Web of Science

See more details