Stains
MGMT

Author: Nat Pernick, M.D. (see Authors page)

Revised: 10 November 2015, last major update November 2013

Copyright: (c) 2002-2015, PathologyOutlines.com, Inc.

PubMed Search: MGMT [title]

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
  • CNS, diffuse glioma and glioblastoma:
  • 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
  • Lung adenocarcinoma
Uses by Pathologists
  • Methylation status may be useful to oncologists planning treatment (see above)
Micro Images

Images hosted on Other servers:

Missing Image

Hepatocellular carcinoma with HIV (fig A/B)

Missing Image

Glioblastoma

Missing Image

Soft tissue sarcoma




Nature images:

Missing Image

Glioblastoma

Missing Image

Soft tissue sarcoma