Sensitive and reproducible method for the determination of MGMT promoter methylation in clinical samples

Simple SummaryContent extracted from patent full text and abstract with AI.

This patent discloses a sensitive and reproducible method for determining the methylation status of the MGMT (O6-methylguanine DNA methyltransferase) gene promoter in clinical samples, such as tumor DNA. The method involves bisulfite treatment of DNA, PCR amplification of targeted MGMT promoter regions, and analysis by techniques such as pyrosequencing or restriction analysis. The degree of MGMT promoter methylation is used as a biomarker to predict response to chemotherapy (with alkylating agents) and as a tool for cancer diagnosis and prognosis. The invention also includes the design of specific primers, amplification products, and kits for use with this method.

Use CasesContent extracted from patent full text and abstract with AI.

• Determining whether a cancer patient (especially with glioblastoma or other tumors) is likely to respond to alkylating chemotherapy agents, such as temozolomide, by measuring MGMT promoter methylation.
• Providing more accurate cancer diagnoses or prognoses by screening for aberrant MGMT methylation in tissue or biopsy samples.
• Enabling retrospective studies on archived clinical samples, including formalin-fixed paraffin-embedded (FFPE) specimens, by robustly analyzing their DNA methylation status.
• Supporting personalized medicine approaches by guiding the selection of cancer treatment regimens based on individual tumor methylation profiles.
• Facilitating large-scale clinical studies or screening programs for cancer patients, owing to the method's scalability and reproducibility.
• Research applications in epigenetics to study MGMT gene regulation and the role of methylation in DNA repair and chemotherapy resistance.

BenefitsContent extracted from patent full text and abstract with AI.

• Higher sensitivity and reproducibility compared to previous methylation-specific PCR (MSP) methods, especially when dealing with low-quality or low-quantity DNA from clinical samples.
• Quantitative, not just qualitative, assessment of methylation at multiple informative CpG sites within the MGMT promoter region.
• Improved predictive power for clinical treatment response (e.g., to alkylating agents) and disease outcome, leading to better-informed therapeutic decisions.
• Robust results even from challenging sample types, including FFPE tissues and archived specimens, expanding the applicability to routine diagnostics and research.
• Availability as a complete kit, including specifically designed primers and reagents, simplifying implementation in clinical laboratories.
• Cost-effective, fast, and easy-to-use method suitable for routine diagnostics and high-throughput sample processing.

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Patent Abstract

The present invention provides a method for determination of the methylation degree of the O 6 -methylguanine DNA methyltransferase gene ( MGMT ) promoter, which is suitable for prediction of the responsiveness of tumors to alkylating agents and for diagnosis or prognosis of cancer. It furthermore provides amplification products and primers which may be used in said method and a kit for performing the method. The method is based on the detection of methylated CpG sites in the MGMT gene.