RT Journal
A1 Halaburkova, Andrea
A1 Cahais, Vincent
A1 Novoloaca, Alexei
A1 Araujo, 
Mariana Gomes da Silva
A1 Khoueiry, Rita
A1 Ghantous, Akram
A1 Herceg, Zdenko
T1 Pan-cancer multi-omics analysis and orthogonal experimental assessment of epigenetic driver genes
JF Genome Research 
JO Genome Research 
YR 2020 
FD October 01 
VO 30 
IS 10 
SP 1517 
OP 1532 
DO 10.1101/gr.268292.120 
UL http://genome.cshlp.org/content/30/10/1517.abstract 
AB The recent identification of recurrently mutated epigenetic regulator genes (ERGs) supports their critical role in tumorigenesis. We conducted a pan-cancer analysis integrating (epi)genome, transcriptome, and DNA methylome alterations in a curated list of 426 ERGs across 33 cancer types, comprising 10,845 tumor and 730 normal tissues. We found that, in addition to mutations, copy number alterations in ERGs were more frequent than previously anticipated and tightly linked to expression aberrations. Novel bioinformatics approaches, integrating the strengths of various driver prediction and multi-omics algorithms, and an orthogonal in vitro screen (CRISPR-Cas9) targeting all ERGs revealed genes with driver roles within and across malignancies and shared driver mechanisms operating across multiple cancer types and hallmarks. This is the largest and most comprehensive analysis thus far; it is also the first experimental effort to specifically identify ERG drivers (epidrivers) and characterize their deregulation and functional impact in oncogenic processes.