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

Cell. Volume 173 Issue 2: p386-399, 5 April 2018 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 analyses, 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.

Data in the GDC

• GDC Manifests
  • Open-Access Data - Download Manifest (3 Files)

Supplemental Data

• MAF Files
  • TCGA somatic mutation data - mc3.v0.2.8.PUBLIC.maf.gz
• Other Data Files
  • TCGA gene expression data - EBPlusPlusAdjustPANCAN_IlluminaHiSeq_RNASeqV2.geneExp.tsv
  • TCGA RPPA data - mdanderson.org_PANCAN_MDA_RPPA_Core.RPPA_whitelisted.tsv

Additional Resources

• Broad Institute FireCloud (link is external) The Broad Institute
• cBioPortal for Cancer Genomics (link is external) Memorial Sloan-Kettering Cancer Center
• NG-CHM (link is external)
• TCPA (link is external)