MGMT promoter methylation determined by HRM in comparison to MSP and pyrosequencing for predicting high-grade glioma response.

作者: Olivier J. Switzeny , Markus Christmann , Mirjam Renovanz , Alf Giese , Clemens Sommer

DOI: 10.1186/S13148-016-0204-7

关键词:

摘要: The DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) causes resistance of cancer cells to alkylating agents and, therefore, is a well-established predictive marker for high-grade gliomas that are routinely treated with drugs. Since MGMT highly epigenetically regulated, the promoter methylation status taken as an indicator silencing, predicting outcome glioma therapy. usually determined by specific PCR (MSP), which labor intensive and error-prone method often used semi-quantitatively. Searching alternatives, we closed-tube high resolution melt (HRM) analysis, quantitative method, compared it MSP pyrosequencing regarding its value. We analyzed glioblastoma cell lines known activity formalin-fixed samples from IDH1 wild-type patients (WHO grade III/IV) radiation temozolomide HRM, MSP, pyrosequencing. data were progression-free survival (PFS) overall (OS) exhibiting methylated unmethylated status. A cut-off level relevant PFS OS was determined. In multivariate Cox regression model, but not found be independent OS. Univariate Kaplan–Meier analyses revealed significant better discrimination between tumors when HRM instead MSP. Compared pyrosequencing, simple, cost effective, accurate fast. at least equivalent in quantifying level. It superior can recommended being determination gliomas.

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