Biological significance of promoter hypermethylation of tumor-related genes in patients with gastric carcinoma.

Background: DNA promoter hypermethylation is a potential means of inactivating tumor-related genes in several types of cancers.

Methods: We investigated aberrant promoter hypermethylation of eleven tumor-related genes in 68 gastric carcinomas and 53 adjacent non-tumor tissues using methylation-specific PCR, and we correlated the findings with clinico-pathological features.

Results: In gastric carcinoma tissues, hypermethylation frequencies of the investigated genes were 61.8% for RASSFIA, 52.9% for APC, 36.8% for MGMT, 30.9% for DAPK, 29.4% for P16, 26.5% for P14, 25% for SHP1, 23.5% for RAR-beta2, 20.6% for GSTP1, 13.2% for TIMP3, and 8.8% for hMLH1. For adjacent non-tumor samples, the frequencies of methylation were respectively 5.7, 37.7, 5.7, 24.5, 3.8, 5.7, 20.8, 5.7, 1.9, 3.8, and 0%. Hypermethylation of P16 correlates with intestinal subtype and cardiac location (P = 0.044 and P = 0.004, respectively), whereas methylation of GSTP1 correlates with diffuse subtype (P = 0.050). Methylation of SHP1 was associated with EBV infection (P = 0.014). Methylation of APC and RAR-beta2 genes were significantly associated with improved patient's outcome (P = 0.007 and P = 0.042, respectively).

Conclusions: Our data suggest that methylation of multiple genes may be involved in the pathogenesis and correlated with the prognosis of gastric carcinomas.