Discovering the Mutational Profile of Early Colorectal Lesions: A Translational Impact

Simple Summary Colorectal cancer (CRC) is one of the most common malignancies worldwide. Next-generation sequencing technologies have identified new candidate genes and deepened the knowledge of the molecular mechanisms underlying the progression of colonic adenomas towards CRC. The main genetic, epigenetic, and molecular alterations driving the onset and progression of CRC in both hereditary and sporadic settings have also been investigated. The evaluation of the CRC risk based on the molecular characterization of early pre-cancerous lesions may contribute to the development of targeted preventive strategies development, help define specific risk profiles, and identify patients who will benefit from targeted endoscopic surveillance. Colorectal cancer (CRC) develops through a multi-step process characterized by the acquisition of multiple somatic mutations in oncogenes and tumor-suppressor genes, epigenetic alterations and genomic instability. These events lead to the progression from precancerous lesions to advanced carcinomas. This process requires several years in a sporadic setting, while occurring at an early age and or faster in patients affected by hereditary CRC-predisposing syndromes. Since advanced CRC is largely untreatable or unresponsive to standard or targeted therapies, the endoscopic treatment of colonic lesions remains the most efficient CRC-preventive strategy. In this review, we discuss recent studies that have assessed the genetic alterations in early colorectal lesions in both hereditary and sporadic settings. Establishing the genetic profile of early colorectal lesions is a critical goal in the development of risk-based preventive strategies.

Automated summary

Colorectal cancer (CRC) is a common malignancy that develops through a multi-step process involving genetic, epigenetic, and molecular alterations. Genetic profiling of early colorectal lesions is essential for developing risk-based preventive strategies in both hereditary and sporadic settings.