Tumor evolution and intratumor heterogeneity in colorectal carcinoma: insights from comparative genomic profiling of primary tumors and matched metastases.

Metastatic colorectal cancer (CRC) is one of the leading causes of cancer-related mortality among men and women worldwide. Over the past few decades, advances in our understanding of the genetic and epigenetic underpinnings of CRC have led to important insights into the pathogenesis of invasive tumors and have identified different molecular subgroups. Nonetheless, the events that might facilitate dissemination of tumor cells to distant sites giving rise to metastatic disease are not well characterized. Furthermore, in contrast to intertumor heterogeneity the extent of intratumor heterogeneity in different types of CRC has not been fully defined. In this paper, we review studies that have compared the genetic profile of primary invasive carcinomas to that of matched metastases and discuss the implications of their findings for our understanding of tumor evolution and for the clinical management of patients with advanced CRC.