Tumor Heterogeneity in Primary Colorectal Cancer and Corresponding Metastases. Does the Apple Fall Far From the Tree?

Colorectal cancer harbors tremendous heterogeneity, with temporal and spatial differences in genetic mutations, epigenetic regulation, and tumor microenvironment. Analyzing the distribution and frequency of genetic, epigenetic, and microenvironment differences within a given tumor and between different sites of a metastatic tumor has been used as a powerful tool to investigate tumorigenesis, tumor progression, and to yield insight into various models of tumor development. A better understanding of tumor heterogeneity would have tremendous clinical relevance, which may manifest most clearly when genetic analyses to inform treatment decisions are performed on a very limited sample of a large tumor. This review summarizes the current concepts of tumor heterogeneity, with a focus on primary colorectal cancers and their corresponding metastases as well as potential clinical implications.