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

Cancer Genome Atlas Research Network

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

Samenvatting

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.

Originele taal-2Engels
Pagina's (van-tot)386-399.e12
TijdschriftCell
Volume173
Nummer van het tijdschrift2
DOI's
StatusGepubliceerd - 5 apr. 2018
Extern gepubliceerdJa

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