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HelpTest Code MGMT MGMT Promoter Methylation, Tumor
Reporting Name
MGMT Promoter Methylation, TumorUseful For
Prognostication of newly diagnosed patients with glioblastoma, IDH-wildtype
Identifying newly diagnosed glioblastoma, IDH-wildtype patients that may respond to alkylating chemotherapy (ie, temozolomide)
Guiding therapy decision making for newly diagnosed glioblastoma, IDH-wildtype in older patients (>60-65 years)
Additional Tests
| Test ID | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| SLIRV | Slide Review in MG | No, (Bill Only) | Yes |
Testing Algorithm
When this test is ordered, slide review will always be performed at an additional charge.
Method Name
Methylation-Specific Polymerase Chain Reaction (PCR) Analysis
Performing Laboratory
Mayo Clinic Laboratories in Rochester
Specimen Type
VariesNecessary Information
Pathology report (final or preliminary), at minimum containing the following information, must accompany specimen for testing to be performed:
1. Patient name
2. Block number-must be on all blocks, slides, and paperwork (can be handwritten on the paperwork)
3. Tissue collection date
4. Source of the tissue
Specimen Required
Preferred:
Specimen Type: Tissue
Container/Tube: Tissue block
Collection Instructions: Submit a formalin-fixed, paraffin-embedded tissue block. At least 40% tumor is required for this assay. In general, a 6 mm x 3 mm area of tissue cut at 5-micron thickness is the minimum amount of tissue needed; this could be collected over multiple slides.
Acceptable:
Specimen Type: Tissue sections
Slides: 1 Stained and 5 unstained
Collection Instructions: Submit 1 slide stained with hematoxylin and eosin and 5 unstained, nonbaked slides with 5-micron thick sections of the tumor. At least 40% tumor is required for this assay. In general, a 6 mm x 3 mm area of tissue cut at 5-micron thickness is the minimum amount of tissue needed; this could be collected over multiple slides.
Specimen Minimum Volume
5 Unstained slides at 5-microns thickness
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Varies | Ambient (preferred) | ||
| Frozen | |||
| Refrigerated | |||
Reject Due To
| Specimens that have been decalcified (all methods) Specimens that have not been formalin-fixed, paraffin-embedded Bone marrow in EDTA |
Reject |
Reference Values
An interpretive report will be provided.
Day(s) Performed
Varies
CPT Code Information
81287
88381
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| MGMT | MGMT Promoter Methylation, Tumor | 60252-4 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| 36734 | Result Summary | 50397-9 |
| 36735 | Result | 60252-4 |
| 36736 | Interpretation | 69047-9 |
| 36737 | Additional Information | 48767-8 |
| 36738 | Specimen | 31208-2 |
| 36739 | Source | 31208-2 |
| 36740 | Tissue ID | 80398-1 |
| 36741 | Released by | 18771-6 |
Highlights
MGMT promoter methylation status has prognostic and predictive value for glioblastoma patients.
Clinical Information
Glioblastoma is the most frequent malignant primary central nervous system (CNS) tumor in adults as originally defined based on morphology. Based on the 2021 World Health Organization (WHO) classification of CNS tumors, the original glioblastoma is now divided in "glioblastoma, IDH-wildtype, CNS WHO grade 4" (most cases) and "astrocytoma, IDH-mutant, CNS WHO grade 4." Current standard of care in both tumor types consists of surgical resection followed by radiotherapy in addition to alkylating chemotherapy with temozolomide.
MGMT (O[6]-methylguanine-DNA methyltransferase) encodes a DNA repair enzyme. This enzyme rescues tumor cells from alkylating agent-induced damage and confers tumor resistance to chemotherapy with alkylating agents. Epigenetic silencing of MGMT by promoter methylation of upstream and downstream CpG sites within differentially methylated regions results in decreased MGMT expression and presumably reduces MGMT-mediated DNA repair of alkylating agent-induced DNA damage in tumor cells.
In newly diagnosed original glioblastoma patients, MGMT promoter methylation has been shown to be a favorable prognostic biomarker and a strong predictor of responsiveness to alkylating chemotherapy. This is particularly relevant for older patients (>60-65 years), who may have decreased tolerance for combined chemoradiation. For this group of patients, MGMT promoter methylation status guides therapy decision making, as MGMT promoter methylation identifies patients who would benefit from monotherapy with the alkylating agent temozolomide instead of radiotherapy alone.
In IDH-mutant diffuse gliomas, MGMT promoter methylation is very frequent and occurs as part of the IDH mutation-induced glioma CpG island methylation phenotype; in infratentorial IDH-mutant astrocytomas, however, MGMT promoter methylation is less common. The prognostic and predictive significance of MGMT promoter methylation status in the context of IDH-mutant tumors is unclear. MGMT promoter methylation is also frequent in "diffuse hemispheric glioma, H3 G34-mutant" and limited data suggest that it is also a favorable prognostic marker in this tumor context.
MGMT promoter methylation status may be evaluated by multiple methods, and the testing platform with most prospective clinical trial validation is methylation-specific polymerase chain reaction evaluating downstream CpG sites.
Interpretation
The interpretation of molecular biomarker analysis includes an overview of the results and the associated diagnostic, prognostic, and therapeutic implications.
Cautions
Test results should be interpreted in context of clinical findings, tumor sampling, and other laboratory data. If results obtained do not match other clinical or laboratory findings, contact the laboratory for possible interpretation. Misinterpretation of results may occur if the information provided is inaccurate or incomplete.
Reliable results are dependent on adequate specimen collection and processing. This test has been validated on formalin-fixed, paraffin-embedded tissues; other types of fixatives are discouraged. Improper treatment of tissues, such as decalcification, may cause polymerase chain reaction failure.
Clinical Reference
1. Hegi ME, Diserens AC, Gorlia T, et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med. 2005;352(10):997-1003
2. Weller M, Stupp R, Reifenberger G, et al. MGMT promoter methylation in malignant gliomas: ready for personalized medicine? Nat Rev Neurol. 2010;6(1):39-51
3. Wick W, Platten M, Meisner C, et al. Temozolomide chemotherapy alone versus radiotherapy alone for malignant astrocytoma in the elderly: The NOA-08 randomised, phase 3 trial. Lancet Oncol. 2012;13(7):707-715
4. Malmstrom A, Gronberg BH, Marosi C, et al. Temozolomide versus standard 6-week radiotherapy versus hypofractionated radiotherapy in patients older than 60 years with glioblastoma: the Nordic randomised, phase 3 trial. Lancet Oncol. 2012;13(9):916-926
5. Korshunov A, Capper D, Reuss D, et al. Histologically distinct neuroepithelial tumors with histone 3 G34 mutation are molecularly similar and comprise a single nosologic entity. Acta Neuropathol. 2016;131(1):137-146
6. Korshunov A, Casalini B, Chavez L, et al. Integrated molecular characterization of IDH-mutant glioblastomas. Neuropathol Appl Neurobiol. 2019;45(2):108-118
7. Mansouri A, Hachem LD, Mansouri S, et al. MGMT promoter methylation status testing to guide therapy for glioblastoma: refining the approach based on emerging evidence and current challenges. Neuro Oncol. 2019;21(2):167-178
8. Banan R, Stichel D, Bleck A, et al. Infratentorial IDH-mutant astrocytoma is a distinct subtype. Acta Neuropathol. 2020;140(4):569-581
9. Wen PY, Weller M, Lee EQ, et al. Glioblastoma in adults: a Society for Neuro-Oncology (SNO) and European Society of Neuro-Oncology (EANO) consensus review on current management and future directions. Neuro Oncol. 2020;22(8):1073-1113
10. WHO Classification of Tumours Editorial Board. Central Nervous System Tumours. 5th ed. IARC Press; 2021. WHO Classification of Tumours, Vol 6
11. Brat DJ, Aldape K, Bridge JA, et al. Molecular biomarker testing for the diagnosis of diffuse gliomas. Arch Pathol Lab Med. 2022;146(5):547-574
Method Description
A real-time methylation-specific polymerase chain reaction assay that evaluates 8 CpG sites (79-86) within the downstream differentially methylated region of the MGMT promoter region.(Ida CM, Butz ML, Jenkins RB, et al. Real-time methylation-specific polymerase chain reaction for MGMT promoter methylation clinical testing in glioblastoma: An alternative detection method for a heterogeneous process. Am J Clin Pathol. 2017;148[4]:296-307)
Report Available
7 to 10 daysSpecimen Retention Time
FFPE tissue block: Unused portions of FPPE blocks will be returned; Unused, unstained slides: 5 years; Stained slides: IndefinitelyTest Classification
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.Forms
If not ordering electronically, complete, print, and send an Oncology Test Request (T729) with the specimen.