Genetic Profiling of Cancers of the Digestive System: Biological Insights and Clinical Implications

Massive parallel sequencing technologies (next-generation sequencing) have enabled us to draw a comprehensive landscape of the genomic aberrations underlying common cancers of the digestive system, and they have thus revolutionized our understanding of the genomic makeup and biology of these tumors. Apart from the commonly mutated founder genes, e.g., KRAS and TP53, we now have detailed information on additional and less frequent genomic events for every major digestive system cancer. However, many challenging issues remain when it comes to translating these findings into clinical applications. Recent examples are the precise definition of the role of genomic heterogeneity and tumor evolution in metastatic spread and their impact on oncologic therapy. Other unresolved issues include the usefulness of identified drivers as novel drug targets and predictive biomarkers, as well as the development of strategies to implement broad genomic testing in individualized patient care. This review aims to dissect and discuss these topics for selected major cancers.