10 Loss of Cyclin D2 Expression in Gastric Cancer

Abstract

This chapter discusses the loss of cyclin D2 expression in gastric cancer. The cyclin D2 promoter methylation is an important regulator of cyclin D2 expression in gastric cancer cells. Promoter hypermethylation is associated with the loss of cyclin D2 expression in gastric cancer cell lines. The density of CpG island methylation has an inverse association with the expression of cyclin D2. Treatment, with 5-azaDC induced demethylation, of the CpG islands, with reactivation of gene expression, in these cyclin D2-negative hypermethylated cell lines. In primary gastric cancer, the majority of tumors, with cyclin D2 promoter, hypermethylation had no cyclin D2 expression, whereas most of the tumors, with unmethylated cyclin D2 promoter, had cyclin D2 expression. The methylation of cyclin D2 promoter region appears to be a tumor-specific event because methylation is detected only in gastric cancer and cancer cell lines but not in any normal gastric mucosa. The detection of cyclin D2 messenger RNA (mRNA) expression, in tumors with promoter hypermethylation, may be related to the extreme sensitivity of methylation-specific polymerase chain reaction (MSP) that can theoretically detect as little as 0.1% of the methylated cells.