Clinical applications of next-generation sequencing in colorectal cancers

Abstract

Like other solid tumors, colorectal cancer (CRC) is a genomic disorder in which various types of genomic alterations, such as point mutations, genomic rearrangements, gene fusions, or chromosomal copy number alterations, can contribute to the initiation and progression of the disease. The advent of a new DNA sequencing technology known as next-generation sequencing (NGS) has revolutionized the speed and throughput of cataloguing such cancer-related genomic alterations. Now the challenge is how to exploit this advanced technology to better understand the underlying molecular mechanism of colorectal carcinogenesis and to identify clinically relevant genetic biomarkers for diagnosis and personalized therapeutics. In this review, we will introduce NGS-based cancer genomics studies focusing on those of CRC, including a recent large-scale report from the Cancer Genome Atlas. We will mainly discuss how NGS-based exome-, whole genome- and methylome-sequencing have extended our understanding of colorectal carcinogenesis. We will also introduce the unique genomic features of CRC discovered by NGS technologies, such as the relationship with bacterial pathogens and the massive genomic rearrangements of chromothripsis. Finally, we will discuss the necessary steps prior to development of a clinical application of NGS-related findings for the advanced management of patients with CRC.

Keywords: Next-generation sequencing; Cancer genomics; Colorectal cancers; Personalized medicine; The cancer genome atlas

Core tip: Next-generation sequencing (NGS)-driven genomic analyses are facilitating the genomic dissection of various types of human cancers, including colorectal cancer (CRC). This review contains an up-to-date summary of recent NGS-based CRC studies and an overview of how these efforts have advanced our understanding of colorectal carcinogenesis with novel biomarkers for genome-based cancer diagnosis and personalized cancer therapeutics.