Recent progress in
cancer genome analysis using next-generation sequencing has revealed a high mutation burden in some
tumors. The particularly high rate of somatic mutation in these
tumors correlates with the generation of neo-
antigens capable of eliciting an immune response. Identification of hypermutated
tumors is therefore clinically valuable for selecting patients suitable for
immunotherapy treatment. There are several known causes of hypermutation in
tumors, such as ultraviolet light in
melanoma, tobacco
smoke in
lung cancer, and excessive APOBEC (
apolipoprotein B mRNA editing enzyme, catalytic
polypeptide-like) activity in breast and
gastric cancer. In
gastrointestinal cancers, one of the leading causes of hypermutation is a defect in DNA mismatch repair, which results in
microsatellite instability (MSI). This review will focus on the frequency, characteristics and genomic signature of hypermutated
gastrointestinal cancers with MSI. Detection of
tumor hypermutation in
cancer is expected to not only predict the clinical benefit of
immune checkpoint inhibitor treatment, but also to provide better surgical strategies for the patients with hypermutated
tumors. Thus, in an era of
precision medicine, identification of hypermutation and MSI will play an important role directing surgical and chemotherapeutic treatment.