Stains & molecular markers
MGMT
Copyright: 2002-2021, PathologyOutlines.com, Inc.
PubMed Search: MGMT [title]
MGMT
Author: Nat Pernick, M.D.
Topic Completed: 1 November 2013
Minor changes: 23 December 2020
Copyright: 2002-2021, PathologyOutlines.com, Inc.
PubMed Search: MGMT [title]
Table of Contents
Definition / general | Pathophysiology | Clinical features | Uses by pathologists | Microscopic (histologic) imagesCite this page: Pernick N. MGMT. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainsmgmt.html. Accessed January 20th, 2021.
Definition / general
- O6-methylguanine-DNA methyltransferase, a DNA repair enzyme at 10q26
- Removes DNA alkylation adducts from mutagenic O(6)-methylguanine, which both:
- Repairs damaged DNA and protects normal cells from carcinogens, and
- Contributes to drug resistance of gliomas to alkylating agents by protecting tumor cells from alkylating agents such as temozolomide
- MGMT promoter hypermethylation and epigenetic silencing often occur as early events in carcinogenesis
- See also CpG island methylation pathway in Colon tumor chapter
Pathophysiology
- Since colon mucosa is exposed directly to environmental carcinogens, maintaining a proficient DNA repair system is important
- MGMT is one of the few proteins to directly remove alkylating agents in the human DNA direct reversal repair pathway
- Promoter (CpG island) hypermethylation leads to silencing of MGMT gene and loss of protein expression
- In colon neoplasia, MGMT methylation can be regarded as an early event or "field defect" (Front Oncol 2013;3:266, DNA Cell Biol 2013;32:371)
Clinical features
- General
- Polymorphisms in MGMT gene may be cancer risk factor (Tumour Biol 2013;34:3227)
- CNS, diffuse glioma and glioblastoma:
- Methylation of promoter region of MGMT is associated with favorable outcome in glioblastoma patients undergoing chemotherapy with alkylating agents (median survival 22 months with versus 13 months without methylated promoter) (Onco Targets Ther 2013;6:1363)
- Methylation may not have favorable outcome in glioblastoma patients >50 years of age (Mod Pathol 2013;26:922), although recommended to consider use of temozolamide in elderly regardless of MGMT status (Clin Neurol Neurosurg 2013;115:1375, PLoS One 2013;8:e74242)
- Can detect MGMT status by either IHC or methylation-specific polymerase chain reaction (Am J Surg Pathol 2013;37:264)
- Methylation of promoter region of MGMT is associated with favorable outcome in glioblastoma patients undergoing chemotherapy with alkylating agents (median survival 22 months with versus 13 months without methylated promoter) (Onco Targets Ther 2013;6:1363)
- Colorectum
- MGMT methylation, found in 40% of colorectal carcinomas, associated primarily with germline C>T SNP (rs16906252) in normal colonic mucosa and colorectal cancer (Mod Pathol 2009;22:1588)
- Also associated with KRAS mutations
- Does NOT have prognostic value for survival (Cancer Causes Control 2011;22:301)
- Promoter CpG island hypermethylation predicts clinical response to dacarbazine in metastatic colorectal cancer (Clin Cancer Res 2013;19:2265)
- Diffuse large B cell lymphoma
- MGMT methylation in 19%, associated with T allele of rs16906252 SNP (Sci Rep 2013;3:2789)
- Lung adenocarcinoma
- The A allele of rs16906252 strongly associated with MGMT methylation (Clin Cancer Res 2011;17:2014)
Uses by pathologists
- Methylation status may be useful to oncologists planning treatment (see above)
Microscopic (histologic) images
Images hosted on other servers:
Hepatocellular carcinoma with HIV (fig A / B)
Glioblastoma
Soft tissue sarcoma
