Genetic Aspects of Gastric Cancer Instability

Unravelling the molecular mechanisms underlying gastric carcinogenesis is one of the major challenges in cancer genomics. Gastric cancer is a very complex and heterogeneous disease, and although much has been learned about the different genetic changes that eventually lead to its development, the detailed mechanisms still remain unclear. Malignant transformation of gastric cells is the consequence of a multistep process involving different genetic and epigenetic changes in numerous genes in combination with host genetic background and environmental factors. The majority of gastric adenocarcinomas are characterized by genetic instability, either microsatellite instability (MSI) or chromosomal instability (CIN). It is believed that chromosome destabilizations occur early in tumour progression. This review summarizes the most common genetic alterations leading to instability in sporadic gastric cancers and its consequences.