Gene

MGMT

O-6-methylguanine-DNA methyltransferase

Explore in graph →CI-GENE-00012512HGNC:7059 ENSG00000170430 NCBI 4255 CIViC Cancer geneApproved

Curated evidence

Clinical evidence (14)

CIViC items involving this gene, grouped by molecular profile and therapy, with native levels and directions. 50 items per page.

civicCuratedShowing 1–14 of 14 evidence items · levels, directions and significance as curated at the source; each row links to its CIViC record.

Therapy	Cancer	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
MGMT Expression1
(prognostic)	GlioblastomaCURATED_BROADER	Prognostic	B	Supports Poor Outcome	3	submitted

Cohorts

Alteration frequency by cohort (0)

Frequency = cases affected / cases profiled within one cohort. Cohorts are never pooled.

Data not yet available

No cohort frequency recorded for this gene.

Literature

Linked publications (9)

25 per page, newest first.

pubmedPublishedShowing 1–9 of 9 publications · bibliographic data as recorded by PubMed; abstracts are not reproduced.

MGMT gene silencing and benefit from temozolomide in glioblastoma.
· N Engl J Med · 2005 · PMID 15758010 · validated civic_curation pubmed
Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents.
· N Engl J Med · 2000 · PMID 11070098 · validated civic_curation pubmed
MGMT promoter methylation is prognostic but not predictive for outcome to adjuvant PCV chemotherapy in anaplastic oligodendroglial tumors: a report from EORTC Brain Tumor Group Study 26951.
· J Clin Oncol · 2009 · PMID 19901104 · validated civic_curation pubmed
The MGMT promoter SNP rs16906252 is a risk factor for MGMT methylation in glioblastoma and is predictive of response to temozolomide.
· Neuro Oncol · 2015 · PMID 25910840 · validated

MGMT Promoter Methylation7
(prognostic)	GlioblastomaCURATED_BROADER	Prognostic	B	Supports Better Outcome	5	accepted	EID491 In patients with glioblastoma, those with methylated MGMT promoters have better overall survival than those with unmethylated promoters. PMID 15758010 · Hegi et al., 2005 · Open in CIViC	civic
〃	GlioblastomaCURATED_BROADER	Prognostic	B	Supports Better Outcome	4	accepted	EID172 MGMT promoter methylation was associated with increased overall and disease-free survival as well as tumor regression in patients with gliomas. PMID 11070098 · Esteller et al., 2000 · Open in CIViC	civic
〃	OligodendrogliomaCURATED_BROADER	Prognostic	B	Supports Better Outcome	4	accepted	EID490 In a study of 152 anaplastic oligodendroglial tumors, 121 samples had MGMT promoter methylation. Those with promoter methylation had better progression-free and overall survival. PMID 19901104 · van den Bent et al., 2009 · Open in CIViC	civic
Carmustine	GlioblastomaCURATED_BROADER	Predictive	B	Supports Sensitivity Response	4	accepted	EID308 MGMT promoter methylation has been shown to confer sensitivity to alkylating agents, such as carmustine, in glioblastoma cells. PMID 11070098 · Esteller et al., 2000 · Open in CIViC	civic
Lomustine + TemozolomideCombination	GlioblastomaCURATED_BROADER	Predictive	A	Supports Sensitivity Response	3	submitted	EID7303 In a small Phase 3 trial, patients with newly diagnosed glioblastoma with methylation of the MGMT promoter randomely assigned to lomustine plus temozolomide in addition to radiotherapy (n=66) or temoz… (full text at CIViC) PMID 30782343 · Herrlinger et al., 2019 · Open in CIViC	civic
O6-Benzylguanine	GlioblastomaCURATED_BROADER	Predictive	E	Supports Sensitivity Response	4	accepted	EID309 In patients lacking MGMT promoter methylation, the use of an MGMT inhibitor, such as O(6)-benzylguanine, in combination with alkylating agents (Carmustine) may be useful in treating patients with init… (full text at CIViC) PMID 11070098 · Esteller et al., 2000 · Open in CIViC	civic
Temozolomide	GlioblastomaCURATED_BROADER	Predictive	A	Supports Sensitivity Response	5	accepted	EID307 In a randomized clinical trial, patients with MGMT promoter methylation benefitted from temozolomide. This benefit was also methylation status dependent, as those without methylation did not see incre… (full text at CIViC) PMID 15758010 · Hegi et al., 2005 · Open in CIViC	civic

MGMT Promoter Methylation7

(prognostic)

GlioblastomaCURATED_BROADER

Prognostic

Supports Better Outcome

accepted

EID491

In patients with glioblastoma, those with methylated MGMT promoters have better overall survival than those with unmethylated promoters.

PMID 15758010 · Hegi et al., 2005 · Open in CIViC

civic

〃

GlioblastomaCURATED_BROADER

Prognostic

Supports Better Outcome

accepted

EID172

MGMT promoter methylation was associated with increased overall and disease-free survival as well as tumor regression in patients with gliomas.

PMID 11070098 · Esteller et al., 2000 · Open in CIViC

civic

〃

OligodendrogliomaCURATED_BROADER

Prognostic

Supports Better Outcome

accepted

EID490

In a study of 152 anaplastic oligodendroglial tumors, 121 samples had MGMT promoter methylation. Those with promoter methylation had better progression-free and overall survival.

PMID 19901104 · van den Bent et al., 2009 · Open in CIViC

civic

Carmustine

GlioblastomaCURATED_BROADER

Predictive

Supports Sensitivity Response

accepted

EID308

MGMT promoter methylation has been shown to confer sensitivity to alkylating agents, such as carmustine, in glioblastoma cells.

PMID 11070098 · Esteller et al., 2000 · Open in CIViC

civic

Lomustine + TemozolomideCombination

GlioblastomaCURATED_BROADER

Predictive

Supports Sensitivity Response

submitted

EID7303

In a small Phase 3 trial, patients with newly diagnosed glioblastoma with methylation of the MGMT promoter randomely assigned to lomustine plus temozolomide in addition to radiotherapy (n=66) or temoz… (full text at CIViC)

PMID 30782343 · Herrlinger et al., 2019 · Open in CIViC

civic

O6-Benzylguanine

GlioblastomaCURATED_BROADER

Predictive

Supports Sensitivity Response

accepted

EID309

In patients lacking MGMT promoter methylation, the use of an MGMT inhibitor, such as O(6)-benzylguanine, in combination with alkylating agents (Carmustine) may be useful in treating patients with init… (full text at CIViC)

PMID 11070098 · Esteller et al., 2000 · Open in CIViC

civic

Temozolomide

GlioblastomaCURATED_BROADER

Predictive

Supports Sensitivity Response

accepted

EID307

In a randomized clinical trial, patients with MGMT promoter methylation benefitted from temozolomide. This benefit was also methylation status dependent, as those without methylation did not see incre… (full text at CIViC)

PMID 15758010 · Hegi et al., 2005 · Open in CIViC

civic

MGMT RS169062521
Temozolomide	GlioblastomaCURATED_BROADER	Predictive	B	Supports Sensitivity Response	3	accepted	EID822 The T allele of the rs16906252 SNP was associated with MGMT methylation and low protein expression. Germline presence of the T allele increased the risk of glioblastoma development (adjusted odds rati… (full text at CIViC) PMID 25910840 · Rapkins et al., 2015 · Open in CIViC	civic

MGMT RS169062521

Temozolomide

GlioblastomaCURATED_BROADER

Predictive

Supports Sensitivity Response

accepted

EID822

The T allele of the rs16906252 SNP was associated with MGMT methylation and low protein expression. Germline presence of the T allele increased the risk of glioblastoma development (adjusted odds rati… (full text at CIViC)

PMID 25910840 · Rapkins et al., 2015 · Open in CIViC

civic

MGMT Underexpression5
Temozolomide	GlioblastomaCURATED_BROADER	Predictive	B	Supports Sensitivity Response	3	accepted	EID2899 In this study, patients with low MGMT expression, compared with patients with high MGMT expression, had a significantly higher response rate (55% v 7%, respectively; P = .004) and improved PFS (median… (full text at CIViC) PMID 17442989 · Chinot et al., 2007 · Open in CIViC	civic
〃	High-Grade Glioma, NOS	Predictive	B	Supports Sensitivity Response	3	accepted	EID2901 This study showed that low MGMT mRNA expression was strongly predictive for prolonged time to progression, treatment response, and length of survival in univariate and multivariate models (p<0.0001). … (full text at CIViC) PMID 21365007 · Kreth et al., 2011 · Open in CIViC	civic
〃	GlioblastomaCURATED_BROADER	Predictive	B	Supports Sensitivity Response	3	accepted	EID2903 In 41 glioblastomas treated with temozolomide (TMZ) therapy (MGMT-immunopositive: n = 22, negative: n = 19), both progression free survival and overall survival were significantly better in MGMT-immun… (full text at CIViC) PMID 21331613 · Watanabe et al., 2011 · Open in CIViC	civic
〃	OligodendrogliomaCURATED_BROADER	Predictive	B	Supports Sensitivity Response	2	accepted	EID2902 In this study, loss of chromosome 1p and low MGMT protein expression were associated with objective response (P < .003 and P < .04, respectively). However, only 54% of the study group had evaluation o… (full text at CIViC) PMID 16541434 · Levin et al., 2006 · Open in CIViC	civic
〃	Neuroendocrine Tumor	Predictive	B	Supports Sensitivity Response	2	accepted	EID2904 Among those patients who received temozolomide-based therapy in this study, the median progression-free survival for patients whose tumors showed intact MGMT expression was 9.3 months compared with 19… (full text at CIViC) PMID 19118063 · Kulke et al., 2009 · Open in CIViC	civic

MGMT Underexpression5

Temozolomide

GlioblastomaCURATED_BROADER

Predictive

Supports Sensitivity Response

accepted

EID2899

In this study, patients with low MGMT expression, compared with patients with high MGMT expression, had a significantly higher response rate (55% v 7%, respectively; P = .004) and improved PFS (median… (full text at CIViC)

PMID 17442989 · Chinot et al., 2007 · Open in CIViC

civic

〃

High-Grade Glioma, NOS

Predictive

Supports Sensitivity Response

accepted

EID2901

This study showed that low MGMT mRNA expression was strongly predictive for prolonged time to progression, treatment response, and length of survival in univariate and multivariate models (p<0.0001). … (full text at CIViC)

PMID 21365007 · Kreth et al., 2011 · Open in CIViC

civic

〃

GlioblastomaCURATED_BROADER

Predictive

Supports Sensitivity Response

accepted

EID2903

In 41 glioblastomas treated with temozolomide (TMZ) therapy (MGMT-immunopositive: n = 22, negative: n = 19), both progression free survival and overall survival were significantly better in MGMT-immun… (full text at CIViC)

PMID 21331613 · Watanabe et al., 2011 · Open in CIViC

civic

〃

OligodendrogliomaCURATED_BROADER

Predictive

Supports Sensitivity Response

accepted

EID2902

In this study, loss of chromosome 1p and low MGMT protein expression were associated with objective response (P < .003 and P < .04, respectively). However, only 54% of the study group had evaluation o… (full text at CIViC)

PMID 16541434 · Levin et al., 2006 · Open in CIViC

civic

〃

Neuroendocrine Tumor

Predictive

Supports Sensitivity Response

accepted

EID2904

Among those patients who received temozolomide-based therapy in this study, the median progression-free survival for patients whose tumors showed intact MGMT expression was 9.3 months compared with 19… (full text at CIViC)

PMID 19118063 · Kulke et al., 2009 · Open in CIViC

civic