Copy Number Alterations as Novel Biomarkers and Therapeutic Targets in Colorectal Cancer

SIMPLE SUMMARY: Copy number alterations (CNAs) occur due to changes to DNA structure that lead to the gain/amplification or loss/deletion of copies of DNA sections from a normal genome. These CNAs have been shown to impact gene expression and appear to play a significant role in the pathogenesis of colorectal cancer; additionally, certain CNAs appear to influence survival as well as response to certain treatments in colorectal cancer. As our understanding of CNAs in colorectal cancer increases, therapeutic options may be developed and implemented to target these CNAs and hopefully improve patient outcomes. The aim of this review is to describe the current methods to detect CNAs and summarize the current literature regarding CNAs and their roles from pathogenesis to prognosis and prediction in colorectal cancer. ABSTRACT: In colorectal cancer, somatic mutations have played an important role as prognostic and predictive biomarkers, with some also functioning as therapeutic targets. Another genetic aberration that has shown significance in colorectal cancer is copy number alterations (CNAs). CNAs occur when a change to the DNA structure propagates gain/amplification or loss/deletion in sections of DNA, which can often lead to changes in protein expression. Multiple techniques have been developed to detect CNAs, including comparative genomic hybridization with microarray, low pass whole genome sequencing, and digital droplet PCR. In this review, we summarize key findings in the literature regarding the role of CNAs in the pathogenesis of colorectal cancer, from adenoma to carcinoma to distant metastasis, and discuss the roles of CNAs as prognostic and predictive biomarkers in colorectal cancer.