@article{d1bb592973c241fca67b3ab54ebef4e1,
title = "A Pan-Cancer Analysis of Enhancer Expression in Nearly 9000 Patient Samples",
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. Causal enhancer-target-gene relationships are inferred from a systematic analysis of 33 cancer types.",
keywords = "PD-L1 expression, The Cancer Genome Atlas, aneuploidy, chromatin state, enhancer expression, mutation burden, pan-cancer analysis, prognostic markers",
author = "Han Chen and Chunyan Li and Xinxin Peng and Zhicheng Zhou and Weinstein, {John N.} and Caesar-Johnson, {Samantha J.} and Demchok, {John A.} and Ina Felau and Melpomeni Kasapi and Ferguson, {Martin L.} and Hutter, {Carolyn M.} and Sofia, {Heidi J.} and Roy Tarnuzzer and Zhining Wang and Liming Yang and Zenklusen, {Jean C.} and Zhang, {Jiashan (Julia)} and Sudha Chudamani and Jia Liu and Laxmi Lolla and Rashi Naresh and Todd Pihl and Qiang Sun and Yunhu Wan and Ye Wu and Juok Cho and Timothy DeFreitas and Scott Frazer and Nils Gehlenborg and Gad Getz and Heiman, {David I.} and Jaegil Kim and Lawrence, {Michael S.} and Pei Lin and Sam Meier and Noble, {Michael S.} and Gordon Saksena and Doug Voet and Hailei Zhang and Brady Bernard and Nyasha Chambwe and Varsha Dhankani and Theo Knijnenburg and Roger Kramer and Kalle Leinonen and Yuexin Liu and Michael Miller and Sheila Reynolds and Ilya Shmulevich and Graham Mann",
note = "Publisher Copyright: {\textcopyright} 2018 The Authors",
year = "2018",
month = apr,
day = "5",
doi = "10.1016/j.cell.2018.03.027",
language = "English",
volume = "173",
pages = "386--399.e12",
journal = "Cell",
issn = "0092-8674",
publisher = "Elsevier B.V.",
number = "2",
}