DNA Methylation in Tumor and Matched Normal Tissues from Non-Small Cell Lung Cancer Patients

Abstract

We used MethyLight assays to analyze DNA methylation status of 27 genes on 49 paired cancerous and noncancerous tissue samples from non-small cell lung cancer (NSCLC) patients who underwent surgical resection. Seven genes (RARB, BVES, CDKN2A, KCNH5, RASSF1, CDH13, and RUNX) were found to be methylated significantly more frequently in tumor tissues than in noncancerous tissues. Only methylation of CCND2 and APC was frequently detected in both cancerous and noncancerous tissues, supporting the hypothesis that the methylation of these two genes is a preneoplastic change and may be associated with tobacco smoking exposure. Methylation of any one of eight genes (RASSF1, DAPK1, BVES, CDH13, MGMT, KCNH5, RARB, or CDH1) was present in 80% of NSCLC tissues but only in 14% of noncancerous tissues. Detection of methylation of these genes in blood might have utility in monitoring and detecting tumor recurrence in earlystage NSCLC after curative surgical resection. (Cancer Epidemiol Biomarkers Prev 2008;17(3):645 -54)

Role of Loss of O6-Methylguanine DNA Methyltransferase (MGMT) Expression in Non-Small Cell Lung Carcinomas (NSCLCs): with Reference to the Relationship with p53 Overexpression

“…have reported that its promoter methylation almost exclusively occurred in tumor cells (6,7). Also, MGMT inactivation through hypermethylation contributes to a large fraction of p53 mutation in NSCLC, including G : C A : T transition (8,9), which is known to be one of the most important tumor suppressor genes in human.…”

“…methylguanine-DNA methyltransferase (MGMT) protect cells from this mutation by transferring the alkyl group from the O 6 -guanine in DNA to an active cysteine within its own sequence (1). Hypermethylation of the promoter region of MGMT gene has been reported to be the most frequent mechanism of MGMT inactivation (2)(3)(4).…”

Concomitant hypermethylation of multiple genes in non-small cell lung cancer (NSCLC)

“…Concomitant methylation of multiple genes is common, particularly in cancerous tissues, which is strongly associated with lung cancer risk [33,34]. In the present study, we identified a panel of the nine hypermethylated genes with excellent specificity and sensitivity, which were only methylated in cancerous tissues but not in noncancerous tissues.…”

Aberrant Expression of E-cadherin in Lung Tissues of Patients with Probable Lung Cancer

“…Hypermethylation of the CDH1 promoter has been postulated to play a critical role in the loss of E-cadherin expression observed in some primary tumors and cell lines without identifying CDH1 mutations. CDH1 promoter hypermethylation has been reported in Non-small cell lung cancer, prostate, thyroid, gastric, and other cancers (Tamura et al, 2000;Feng et al, 2008;Ramezani et al, 2012). The finding that treatment of cell lines with demethylating agents can, in some cases, restore E-cadherin expression suggests that in some tumors, promoter hypermethylation plays an important role in silencing of CDH1 expression.…”