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Test Code MGMTD MGMT Promoter Methylation Analysis, Tumor


Necessary Information


A pathology report (final or preliminary), containing the following information, is required and 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


This assay requires at least 20% tumor nuclei.

-Preferred amount of tumor area with sufficient percent tumor nuclei: tissue 144 mm(2) tissue (4 x 6 mm x 6 mm areas)

-Minimum amount of tumor area: 36 mm(2) tissue (1 x 6 mm x 6 mm area)

-These amounts are cumulative over up to 10 unstained slides and must have adequate percent tumor nuclei.

-Tissue fixation: formalin-fixed paraffin-embedded (FFPE), non-decalcified

 

Submit only 1 of the following specimens:

 

Specimen Type: Tissue block

Collection Instructions: Submit a formalin-fixed non-decalcified, paraffin-embedded tissue block.

 

Specimen Type: Tissue slide

Slides: 1 Stained and 10 unstained

Collection Instructions: Submit 1 slide stained with hematoxylin and eosin and 10 unstained, nonbaked slides with 5-micron thick sections of the tumor tissue.

Note: The total amount of required tumor nuclei can be obtained by scraping up to 10 slides from the same block.


Useful For

Prognostication of newly diagnosed patients with glioblastoma

 

Identification of newly diagnosed glioblastoma patients that may derive benefit from alkylating chemotherapy (ie, temozolomide)

 

Therapy selection for newly diagnosed glioblastoma in older patients (>60-65 years)

Method Name

Droplet Digital Polymerase Chain Reaction (ddPCR)

Reporting Name

MGMT Promoter Methylation Analysis

Specimen Type

Varies

Specimen Minimum Volume

5 unstained slides at 5-microns thickness

Specimen Stability Information

Specimen Type Temperature Time
Varies Ambient (preferred)
  Refrigerated 

Reject Due To

Specimens that have been decalcified (all methods)
Specimens that have not been formalin-fixed, paraffin-embedded
Extracted nucleic acid (DNA/RNA)		 Reject

Clinical Information

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 increased methylation of CpG sites within the promoter region results in decreased MGMT expression and reduces MGMT-mediated DNA repair of alkylating agent-induced DNA damage in tumor cells, increasing tumor sensitivity and response to alkylating chemotherapy.

 

MGMT promoter methylation status is a molecular biomarker for glioblastoma, which is the most frequent malignant primary central nervous system (CNS) adult-type tumor. In newly diagnosed patients with glioblastoma, MGMT promoter "methylated" status indicating increased levels of methylation is an independent favorable prognostic biomarker and a strong predictor of response to alkylating chemotherapy. Current standard of care treatment for glioblastoma patients consists of surgical resection followed by radiotherapy and alkylating chemotherapy with temozolomide. Older patients (>60-65 years) often have decreased tolerance for combined chemoradiation. For this group of patients, MGMT promoter methylation status guides treatment decision between monotherapy with the alkylating agent temozolomide versus radiotherapy alone.

 

Glioblastoma was originally defined solely based on histological features. 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".(1) In isocitrate dehydrogenase (IDH)-mutant diffuse gliomas, MGMT promoter "methylated" status is frequent and strongly associated with the IDH mutation-induced glioma CpG island methylator phenotype (G-CIMP), except for the uncommon infratentorial IDH-mutant astrocytomas. Therefore, the clinical significance of MGMT promoter methylation status in the context of IDH-mutant diffuse gliomas is less firmly established.

 

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

An interpretive report will be provided.

Day(s) Performed

Varies

Report Available

7 to 10 days

Performing Laboratory

Mayo Clinic Laboratories in Rochester

Test 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.

CPT Code Information

81287

88381-Microdissection manual