Evidence map›Paper›PMID 14712205›Full record

ReviewOncogene2004

Generating mutations but providing chemosensitivity: the role of O6-methylguanine DNA methyltransferase in human cancer.

Manel Esteller, James G Herman

2 registry-linked trialsAbstract readReview
PubMed Publisher
In one paragraph

Review in Oncogene, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 99 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
99citing papers in PubMed, 5 pooled it
10.9field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03832621 phase2completednot on this mapstarted 2019, after this paper: background citation

NIVOLUMAB Plus IPILIMUMAB and TEMOZOLOMIDE in Combination in Microsatellite Stable (MSS), MGMT Silenced Metastatic Colorectal Cancer (mCRC): the MAYA Study

TypeinterventionalSponsorFondazione IRCCS Istituto Nazionale dei Tumori, MilanoRan2019 to 2021Enrolled135ConditionsMetastatic Colorectal CancerArmsTemozolomide, Nivolumab, Ipilimumab
NCT04689347 phase1 / phase2recruitingnot on this mapstarted 2021, after this paper: background citation

Phase 1b/2 Trial of 5-fluorouracil, Leucovorin, Irinotecan in Combination With Temozolomide (FLIRT) and Bevacizumab for the First-line Treatment of Patients With MGMT Silenced, Microsatellite Stable Metastatic Colorectal Cancer.

TypeinterventionalSponsorFondazione IRCCS Istituto Nazionale dei Tumori, MilanoRan2021 to 2027Enrolled27ConditionsMetastatic Colorectal CancerArmsBevacizumab, Irinotecan, Leucovorin, 5Fluorouracil, Temozolomide
3 · Its place in the literature

Who cites it

99 citing papers in PubMed, 5 syntheses or guidelines pooled it, 322 citations in OpenAlex.

  1. Clinically Relevant Imaging Features forAJNR. American journal of neuroradiology · 2018
    Pooled it
  2. Prognosis value of MGMT promoter methylation for patients with lung cancer: a meta-analysis.International journal of clinical and experimental pathology · 2015
    Pooled it
  3. Two DNA repair gene polymorphisms on the risk of gastrointestinal cancers: a meta-analysis.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014
    Pooled it
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  16. Epigenetic downregulation of OEnvironmental pollution (Barking, Essex : 1987) · 2024
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39 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

2 authors at 2 institutions in 2 countries.

Manel EstellerCancer Epigenetics Laboratory, Molecular Pathology Program, Spanish National Cancer Center (CNIO), Melchor Fernandez Almagro 3, Madrid 28029, Spain. mesteller@cnio.es
James G Herman
Sidney Kimmel Comprehensive Cancer Center · USSpanish National Cancer Research Centre · ES

Funding

INTEGRATED DEVELOPMENT OF NOVEL MOLECULAR MARKERSU01CA084986 · NCI · JOHNS HOPKINS UNIVERSITY · PI SIDRANSKY, DAVID · 1999 to 2014
$33.8M
TARGETING EARLY CHANGES FOR NEW SCREENING STRATEGIESP50CA058184 · NCI · JOHNS HOPKINS UNIVERSITY · PI BISWAL, SHYAM · 1992 to 2013
$30.5M
NCI NIH HHS CA84986NCI NIH HHS P50CA58184
6 · The paper itself

Abstract

O(6)-methylguanine DNA methyltransferase (MGMT) is a key enzyme in the DNA repair network. MGMT removes mutagenic and cytotoxic adducts from O(6)-guanine in DNA, the preferred point of attack of many carcinogens (i.e. methylnitrosourea) and alkylating chemotherapeutic agents (i.e. BCNU, temozolamide, etc.). Hypermethylation of the CpG island located in the promoter region of MGMT is primarily responsible for the loss of MGMT function in many tumor types. The methylation-mediated silencing of MGMT has two consequences for cancer. First, tumors with MGMT methylation have a new mutator phenotype characterized by the generation of transition point mutations in genes involved in cancer etiology, such as the tumor suppressor p53 and the oncogene K-ras. Second, MGMT hypermethylation demonstrates the possibility of pharmacoepigenomics: methylated tumors are more sensitive to the killing effects of alkylating drugs used in chemotherapy. These recent results underscore the importance of MGMT in basic and translational cancer research.

Indexed as

MutationAntineoplastic Agents, AlkylatingDNA MethylationGene SilencingHumansNeoplasmsO(6)-Methylguanine-DNA MethyltransferasePromoter Regions, GeneticAntineoplastic Agents, AlkylatingO(6)-Methylguanine-DNA Methyltransferase

Identifiers

PMID14712205
OpenAlexW2078640192

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.