CpG Island Methylation of the MLH1, MGMT, DAPK, and CASP8 Genes in Cancerous and Adjacent Noncancerous Stomach Tissues

Abstract

Background and Objective. Many factors are involved in the development of gastric adenocarcinoma. The CpG island methylation of apoptosis and mismatch repair genes by the loss of their function is important in gastric adenocarcinoma. The aim of this study was to determine the methylation frequency of MLH1, MGMT, CASP8, and DAPK in cancerous and adjacent noncancerous stomach tissues, to determine possible associations with the selected clinicopathological characteristics, and to identify possible correlation between the methylation of individual genes. Material and Methods. The methylation status of MLH1, MGMT, DAPK, and CASP8 was investigated in 69 patients with gastric adenocarcinoma by using methylation-specific polymerase chain reaction. The associations between patients’ clinical characteristics and methylation status were assessed. Results. The methylation frequency of the MLH1, DAPK, MGMT, and CASP8 gene promoters in cancerous and adjacent noncancerous tissues was 31.9% and 27.5%; 47.8% and 46.4%; 36.2% and 44.9%; and 5.8% and 5.8%, respectively, but the differences were not significant. There was no significant association between the methylation status of the mentioned genes and clinicopathological characteristics, such as age, sex, tumor type by the Lauren classification, degree of differentiation G, and TNM staging. An inverse correlation between the methylation of the DAPK and MLH1 gene promoters in cancerous and surrounding noncancerous tissues was found. Conclusions. The methylation of the MLH1, MGMT, DAPK, and CASP8 genes was found to occur both in cancerous and noncancerous stomach tissues. These findings provide additional insights into gene methylation patterns in gastric adenocarcinoma.

Role of P14 and MGMT Gene Methylation in Hepatocellular Carcinomas: a Meta-analysis

“…Gu et al (2013) performed a meta-analysis that identified a strong relationship between MGMT methylation and the risk of non-small-cell lung cancer, with MGMT methylation much higher in cancer than in non-cancer tissues. In contrast, Kupcinskaite-Noreikiene et al (2013) reported that MGMT methylation was lower in gastric carcinoma than in adjacent tissues. Moreover, Laing et al (2010) found no relationship between MGMT methylation and cutaneous squamous cell carcinoma (p=0.21).…”

Clinical effect of DAPK promoter methylation in gastric cancer

“…[ 24–27 29 30 33–36 38–45 ] Fifteen studies comprising 813 male and 391 female GC patients investigated the relationship between DAPK promoter methylation and gender status. [ 24 25 27–29 31 32 34 36–38 40–42 44 ] Nine studies comprising 235 early GC patients and 468 advanced GC patients investigated the association between DAPK promoter methylation and tumor stage. [ 24 27–29 31 32 36 38 44 ] Twelve studies involving 607 lymph node-positive patients and 301 lymph node-negative patients investigated the association between DAPK promoter methylation and lymph node status.…”

“…[ 40 41 ] Three studies reported that DAPK promoter methylation had a similar level in GC and in nonmalignant tissues. [ 25 34 45 ] The remaining other studies reported that DAPK promoter methylation had a relatively higher frequency in GC than in nonmalignant samples. [ 24 26 27 29 30 33 35 36 38 39 42–44 ] Thus, we first determined whether DAPK promoter methylation was significantly correlated with the risk of GC.…”

Effect of DR4 promoter methylation on the TRAIL-induced apoptosis in lung squamous carcinoma cell

“…The gene promoter region CpG island is generally found in the non-methylation status. An abnormally high expression can directly or indirectly block gene transcription, resulting in silencing or a function of the cell cycle regulatory gene, DNA repair gene, apoptosis gene, tumor suppressor gene and other related genes, which may be one of the main factors inducing tumors (29,30). In lung carcinoma and other carcinoma cells, the abnormal increase in the methylation levels of some gene CpG island regions is their main characteristic (31).…”