Test Id : MGMT
MGMT Promoter Methylation, Tumor
Useful For
Suggests clinical disorders or settings where the test may be helpful
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)
Highlights
MGMT promoter methylation status has prognostic and predictive value for glioblastoma patients
Additional Tests
Lists tests that are always performed, at an additional charge, with the initial tests.
| Test Id | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| SLIRV | Slide Review in MG | No, (Bill Only) | Yes |
Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.
When this test is ordered, slide review will always be performed at an additional charge.
Method Name
A short description of the method used to perform the test
Methylation-Specific Polymerase Chain Reaction (PCR) Analysis
NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.
Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test
Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.
When this test is ordered, slide review will always be performed at an additional charge.
Specimen Type
Describes the specimen type validated for testing
Varies
Necessary 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
Defines the optimal specimen required to perform the test and the preferred volume to complete testing
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.
Forms
If not ordering electronically, complete, print, and send an Oncology Test Request (T729) with the specimen.
Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the testing laboratory. The minimum volume is sufficient for one attempt at testing.
5 Unstained slides at 5-microns thickness
Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected
| Specimens that have been decalcified (all methods) Specimens that have not been formalin-fixed, paraffin-embedded Bone marrow in EDTA | Reject |
Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Varies | Ambient (preferred) | ||
| Refrigerated | |||
| Frozen | |||
Useful For
Suggests clinical disorders or settings where the test may be helpful
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)
Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.
When this test is ordered, slide review will always be performed at an additional charge.
Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
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.
Reference Values
Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
An interpretive report will be provided.
Interpretation
Provides information to assist in interpretation of the test results
The interpretation of molecular biomarker analysis includes an overview of the results and the associated diagnostic, prognostic, and therapeutic implications.
Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
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
Recommendations for in-depth reading of a clinical nature
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
Describes how the test is performed and provides a method-specific reference
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)
PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information
Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.
Varies
Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.
Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location
Indicates the location of the laboratory that performs the test
Fees :
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.
- Authorized users can sign in to Test Prices for detailed fee information.
- Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
- Prospective clients should contact their account representative. For assistance, contact Customer Service.
Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.
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.
CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
CPT codes are provided by the performing laboratory.
CPT codes are provided by the performing laboratory.
81287
88381
LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.
| Test Id | Test Order Name | Order LOINC Value |
|---|---|---|
| MGMT | MGMT Promoter Methylation, Tumor | 60252-4 |
| Result Id | Test Result Name |
Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
|
|---|---|---|
| 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 |