Tumor suppressor genes and DNA repair genes can be inactivated not only by genetic lesions, like mutations or deletions, but also by aberrant DNA methylation of promoter regions. These DNA methylation alterations may serve as biomarkers for early detection, refinement of diagnosis, prognosis, or prediction of therapy response. Despite a long history of DNA methylation research in the field of oncology so far only very few aberrant DNA methylation events are of proven and generally accepted clinical value and are part of the routine diagnostic work‑up of cancer patient samples. Hypermethylation of the MGMT gene promoter in glioblastoma is one of the very few DNA methylation biomarkers that has entered routine clinical diagnostics. In this very aggressive primary brain tumor it is associated with an overall better prognosis and a better response to alkylating therapy. This narrative review provides an overview about the underlying biology, the methodological challenges, and the clinical utility of MGMT promoter methylation, primarily in the context of glioblastoma. Emerging applications in other cancer types are also summarized and discussed. Throughout the review the focus is more on a critical discussion of concepts and relevant publications and their merits and shortcomings than trying to achieve complete coverage of the voluminous literature.
Ulrich Lehmann (Wed,) studied this question.