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  • Title: Quantitative O(6)-methylguanine DNA methyltransferase methylation analysis in curatively resected non-small cell lung cancer: associations with clinical outcome.
    Author: Brabender J, Usadel H, Metzger R, Schneider PM, Park J, Salonga D, Tsao-Wei DD, Groshen S, Lord RV, Takebe N, Schneider S, Hölscher AH, Danenberg KD, Danenberg PV.
    Journal: Clin Cancer Res; 2003 Jan; 9(1):223-7. PubMed ID: 12538473.
    Abstract:
    PURPOSE: Hypermethylation of the O(6)-methylguanine DNA methyltransferase (MGMT) promoter region leads to transcriptional repression of the MGMT gene and is a common event in primary human neoplasia. The purpose of this study was to determine the frequency and clinical relevance of MGMT gene promoter hypermethylation in curatively resected non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: MGMT hypermethylation, expressed as the ratio between methylated MGMT to unmethylated MYOD1 in genomic DNA, was analyzed in normal and matching tumor tissue from 90 patients with NSCLC, and a control group of 10 patients without cancer using a methylation-specific fluorogenic Real-Time PCR (Taqman) system. RESULTS: Hypermethylation of the MGMT promoter was detected in 34 of 90 (38%) tumor specimens and 16 of 90 (18%) matching normal lung tissues of patients with NSCLC, and in 0 (0%) cases of the control group without lung cancer. The mean MGMT methylation level was significantly higher in tumor than in matching normal tissue (P < 0.001). MGMT methylation in normal tissue was always accompanied with MGMT methylation in matching tumor tissue. Patients without MGMT promoter hypermethylation showed a significantly better survival than patients with MGMT promoter hypermethylation (P = 0.017). Multivariate analysis revealed MGMT promoter methylation as an independent unfavorable prognostic factor (P = 0.030). CONCLUSIONS: MGMT promoter hypermethylation is a common event in patients with primary NSCLC. This epigenetic alteration is associated with inferior survival, suggesting that MGMT promoter hypermethylation might be an important biomarker for a biological aggressive disease in NSCLC.
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