Putative cis-regulatory drivers in colorectal cancer

Examination of allele-specific expression identifies 71 genes with excess somatic cis -regulatory effects in colorectal cancer (CRC), and 1,693 and 948 expression quantitative trait loci (eQTLs) in normal samples and tumours, respectively (with 36% of tumour eQTLs exclusive to CRC); tumour-specific eQTLs are more enriched for low CRC genome-wide association study P values and accumulate more somatic mutations than shared eQTLs, suggesting a role as germline-derived cancer regulatory drivers. Transcriptome characteristics of colorectal cancer This paper presents a comprehensive overview of the transcriptome alterations and changes in the regulatory landscape associated with colorectal cancer tumorigenesis. Using RNA sequencing of 103 matched tumour and normal colon mucosa samples from patients with colorectal cancer, and investigating allele-specific expression, the authors show that germline genotypes remain important determinants of allelic gene expression in tumours and identify 71 genes with excess of somatic cis -regulatory effects in colorectal cancer, suggesting a cancer driver role. New expression quantitative trait loci (eQTLs) are identified, 36% of which are exclusive to colorectal cancer. Additional evidence indicates that tumour-specific eQTL genes constitute germline-derived cancer regulatory drivers. The cis- regulatory effects responsible for cancer development have not been as extensively studied as the perturbations of the protein coding genome in tumorigenesis 1 , 2 . To better characterize colorectal cancer (CRC) development we conducted an RNA-sequencing experiment of 103 matched tumour and normal colon mucosa samples from Danish CRC patients, 90 of which were germline-genotyped. By investigating allele-specific expression (ASE) we show that the germline genotypes remain important determinants of allelic gene expression in tumours. Using the changes in ASE in matched pairs of samples we discover 71 genes with excess of somatic cis- regulatory effects in CRC, suggesting a cancer driver role. We correlate genotypes and gene expression to identify expression quantitative trait loci (eQTLs) and find 1,693 and 948 eQTLs in normal samples and tumours, respectively. We estimate that 36% of the tumour eQTLs are exclusive to CRC and show that this specificity is partially driven by increased expression of specific transcription factors and changes in methylation patterns. We show that tumour-specific eQTLs are more enriched for low CRC genome-wi