Mutational and expressional analyses of ATG5, an autophagy-related gene, in gastrointestinal cancers

There is mounting evidence that alterations of cell death processes are involved in cancer pathogenesis. ATG5 is a key regulator of autophagic and apoptotic cell death. The aim of this study was to see whether alterations of ATG5 protein expression and somatic mutation of ATG5 gene are features of human gastrointestinal cancers. In this study, we analyzed ATG5 somatic mutation in 45 gastric, 45 colorectal, and 45 hepatocellular carcinomas by single-strand conformation polymorphism (SSCP). Also, we analyzed ATG5 protein expression in 100 gastric, as well as in 95 colorectal and hepatocellular carcinomas using immunohistochemistry. Overall, we detected two somatic missense mutations of ATG5 gene in the coding sequences p.Leu112Phe and p.His41Tyr. The mutations were observed in one gastric and one hepatocellular carcinoma. Immunohistochemically, ATG5 protein was well expressed in normal stomach, colon, and liver epithelial cells, while it was lost in 21 (21%) of the gastric carcinomas, in 22 (23%) of the colorectal carcinomas, and in 5 (10%) of the hepatocellular carcinomas. Our data suggest that ATG5 gene could be altered in gastrointestinal cancers at the mutational or expressional level. Despite the low incidences of the alterations, our data led us to conclude that somatic mutation and loss of expression of ATG5 gene might play a role in gastrointestinal cancer pathogenesis by altering autophagic and apoptotic cell death.