Genomic approach to translational studies in colorectal cancer

Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide. The pathogenesis of CRC is complex with molecular subtypes defined by pathways of sequential (epi-) genetic alterations and different forms of genomic instability. The management of CRC has evolved considerably over the past decade, consisting of surgery and treatment with radiation, chemotherapy or molecularly targeted agents. Population screening is progressively being introduced for early detection of disease. Decisions to use a particular treatment are principally related to primary site, TNM stage and comorbidity of the patient. Advances in the development of microarray and next-generation sequencing (NGS) technologies have enabled the possibility of personalized medicine for CRC, revolutionizing our knowledge of tumor biology, identifying prognostic and predictive biomarkers, and contributing new tools for diagnosis and surveillance. Genomic studies have identified new cancer driver genes and druggable targets, revealed substantial inter- and intra-tumor (epi-) genetic heterogeneity, and highlighted the importance of cell-of-origin, differentiation hierarchy, phenotypic plasticity and stromal contribution for tumor clinical behavior. Here, we review results of recent translational studies of the CRC genome, transcriptome, methylome and miRNAome, with a focus on tumor classification, diagnostic, prognostic and predictive findings.