W. Rathmell
Last active: 11/27/2019

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

Chen H, Li C, Peng X, Zhou Z, Weinstein JN, Cancer Genome Atlas Research Network, Liang H
Cell. 2018 173 (2): 386-399.e12

PMID: 29625054 · PMCID: PMC5890960 · DOI:10.1016/j.cell.2018.03.027

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.

Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

MeSH Terms (11)

Aneuploidy B7-H1 Antigen Chromatin Databases, Genetic Enhancer Elements, Genetic Gene Expression Regulation, Neoplastic Humans Immunotherapy Neoplasms Sequence Analysis, RNA Survival Rate

Connections (1)

This publication is referenced by other Labnodes entities:

Links