title: The role of MGMT testing in clinical practice: a report of the association for molecular pathology.
abstract: Recent advances in modern molecular technologies allow for the examination and measurement of cancer-related genomic changes. The number of molecular tests for evaluation of diagnostic, prognostic, or predictive markers is expected to increase. In recent years, O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation has been firmly established as a biomarker in patients diagnosed with gliomas, for both clinical trials and routine clinical management. Similarly, molecular markers, such as loss of heterozygosity (LOH) for 1p/19q have already demonstrated clinical utility in treatment of oligodendroglial tumors, and others might soon show clinical utility. Furthermore, nonrandom associations are being discovered among MGMT, 1p/19q LOH, isocitrate dehydrogenase (IDH) mutations, and other tumor-specific modifications that could possibly enhance our ability to predict outcome and response to therapy. While pathologists are facing new and more complicated requests for clinical genomic testing, clinicians are challenged with increasing numbers of molecular data coming from molecular pathology and genomic medicine. Both pathologists and oncologists need to understand the clinical utility of molecular tests and test results, including issues of turnaround time, and their impact on the application of targeted treatment regimens. This review summarizes the existing data that support the rationale for MGMT promoter methylation testing and possibly other molecular testing in clinically defined glioma subtypes. Various molecular testing platforms for evaluation of MGMT methylation status are also discussed.
authors.affiliation: Department of Pathology, Henry Ford Hospital, Detroit, Michigan, USA. mcankov1@hfhs.org
authors.forename: Milena
authors.initials: M
authors.lastname: Cankovic
authors.forename: Marina N
authors.initials: MN
authors.lastname: Nikiforova
authors.forename: Matija
authors.initials: M
authors.lastname: Snuderl
authors.forename: Adekunle M
authors.initials: AM
authors.lastname: Adesina
authors.forename: Neal
authors.initials: N
authors.lastname: Lindeman
authors.forename: Patrick Y
authors.initials: PY
authors.lastname: Wen
authors.forename: Eudocia Q
authors.initials: EQ
authors.lastname: Lee
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D018899:CpG Islands; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D020868:Gene Silencing; D005820:Genetic Testing; D005910:Glioma / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics; D006801:Humans; D010641:Phenotype; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes