Transcriptome Analyses Identify Deregulated MYC in Early Onset Colorectal Cancer

Abstract

Despite a global decrease in colorectal cancer (CRC) incidence, the prevalence of early-onset colorectal cancer (EOCRC), or those occurring in individuals before the age of 50, has steadily increased over the past several decades. When compared to later onset colorectal cancer (LOCRC) in individuals over 50, our understanding of the genetic and molecular underpinnings of EOCRCs is limited. Here, we conducted transcriptomic analyses of patient-matched normal colonic segments and tumors to identify gene expression programs involved in carcinogenesis. Amongst differentially expressed genes, we found increased expression of the <i>c-MYC</i> proto-oncogene (<i>MYC</i>) and its downstream targets in tumor samples. We identified tumors with high and low differential <i>MYC</i> expression and found patients with high-<i>MYC</i> tumors were older and overweight or obese. We also detected elevated expression of the <i>PVT1</i> long-non-coding RNA (lncRNA) in most tumors and found gains in copy number for both <i>MYC</i> and <i>PVT1</i> gene loci in 35% of tumors evaluated. Our transcriptome analyses indicate that EOCRC can be sub-classified into groups based on differential <i>MYC</i> expression and suggest that deregulated <i>MYC</i> contributes to CRCs that develop in younger patients.