This test is intended to detect IDH1 or IDH2 mutations within glioma or suspected glioma specimens.
IDH1 and IDH2 encode the cytoplasmic and mitochondrial isocitrate dehydrogenase enzymes that normally convert isocitrate into alpha-ketoglutarate. Mutations affecting arginine residues in these proteins result in the production of 2-hydroxyglutarate which functions as an oncometabolite. 2-hydroxyglutarate inhibits alpha-ketoglutarate dependent dioxygenases such as TET enzymes, leading to global DNA and histone methylation changes.
Mutation status for IDH1 and IDH2 determines the final classification of diffuse astrocytic and oligodendroglial tumors according to the World Health Organization Classification of Tumors of the Central Nervous System. IDH mutations in glioma (most frequently IDH1 R132H) impart a significantly better prognosis than grade-matched IDH wild-type gliomas and these mutations are associated with superior response to chemotherapy. These mutations can be associated with 1p/19q co-deletion and/or MGMT promoter methylation.
Interpretive report provided.
This test will only detect mutations within specific gene regions and specific gene fusions (see University of Michigan Pathology Handbook for specific information). This test may fail to detect molecular alterations below the limit of detection of this assay (approximately 5%). This test cannot definitively distinguish between somatic and germline variants. The clinical implications of the findings in this report may change based on evolution of the scientific literature.
For formalin-fixed, paraffin-embedded tissue, a block containing an area with a high percentage of neoplastic cells (for micro-/macro-dissection) is preferred. Unstained, UNBAKED slides (5-8, 10-micron slides; 10-15 if few neoplastic cells are present) with associated H&E stained slide are also acceptable. Decalcified tissue or other fixatives will be accepted and the assay attempted, however these may result in failed testing due to degraded nucleic acid. Both blocks and slides should be stored at room temperature. A Diff-Quik or Papanicolaou stained aspirate smear (preferable containing a high percentage and overall amount of neoplastic cells) is also acceptable. Store at room temperature.
Previously extracted DNA from a CLIA certified laboratory may be accepted; however, the extracting laboratory must take responsibility for ensuring that viable, neoplastic cells comprise at least 10% of cellularity within the extracted sample.
By ordering this test the clinician acknowledges that informed consent has been obtained from the patient as required by applicable state or federal laws and the ordering clinician has authorization from the patient permitting MLabs to report the test results to the ordering clinician. Test includes microdissection billed as a separate additional charge. Test includes pathologist interpretation of results billed as a separate additional charge. This test is not available without interpretation.