Molecular carcinogenesis of gastric cancer: Lauren classification, mucin phenotype expression, and cancer stem cells

AbstractGastric cancer (GC), one of the most common human cancers, is a heterogeneous disease with different phenotypes, prognoses, and responses to treatment. Understanding the pathogenesis of GC at the molecular level is important for prognosis prediction and determining treatments. Microsatellite instability (MSI), silencing ofMLH1,MGMT, andCDKN2A genes by DNA hypermethylation,KRAS mutation,APC mutation, andERBB2 amplification are frequently found in intestinal type GC. Inactivation ofCDH1 andRARB by DNA hypermethylation, and amplification ofFGFR andMET, are frequently detected in diffuse type GC. In addition,BST2 andPCDHB9 genes are overexpressed in intestinal type GC. Both genes are associated with GC progression. GC can be divided into gastric/intestinal mucin phenotypes according to mucin expression. MSI, alterations ofTP73,CDH1 mutation, and DNA methylation ofMLH are detected frequently in the gastric mucin phenotype.TP53 mutation, deletion ofAPC, and DNA methylation ofMGMT are detected frequently in the intestinal mucin phenotype.FKTN is overexpressed in the intestinal mucin phenotype, andIQGAP3 is overexpressed in the gastric mucin phenotype. These genes are involved in GC progression. To characterize cancer stem cells, a useful method is spheroid colony formation.KIFC1 andKIF11 genes show more than twofold higher expression in spheroid-forming cells than that in parental cells. BothKIF genes are overexpressed in GC, and knockdown of these genes inhibits spheroid fo...
Source: International Journal of Clinical Oncology - Category: Cancer & Oncology Source Type: research