Clinical oncogenomics and personalized medicine in colorectal cancer for the surgeon: what we need to know and what the future holds

Changes in the normal nucleotide sequence of the human genome plays an integral part in the development and progression of all cancers. It is now recognized that certain genomic alterations can be used to determine prognosis and potential response to treatment for patients diagnosed with a range of cancers. Breast cancer is perhaps the best example of how gene expression analysis can infuence treatment choices and potentially prevent patients from receiving adjuvant chemotherapy that would have a negligible beneft. It is becoming increasingly likely that most, if not all, tumors will be subjected to some form of genomic analysis in the future in an attempt to provide patients with a personalized treatment plan that maximizes efficacy and reduces toxicity. This paper gives a brief history of genomic sequencing followed by a description of clinically relevant oncogenomics for those working in the colorectal cancer feld. The relevance of RAS, BRAF, mismatch repair, and microsatellite instability status are discussed in detail. Potential implications of PIK3CA mutations are briefy described. It fnishes by providing a summary of more complex techniques such as whole exome and whole genome sequencing, some of which may be used in the clinical setting and some of which will be reserved solely for novel target and biomarker identifcation in the academic setting.  An understanding of the molecular mechanisms that underlie the development and progression of colorectal cancer is necessary and will become more relevant as the practice of personalized medicine is more widely implemented.