Evidence map›Paper›PMID 9271436›Full record

ArticleMolecular and cellular biology1997

Methylation of discrete regions of the O6-methylguanine DNA methyltransferase (MGMT) CpG island is associated with heterochromatinization of the MGMT transcription start site and silencing of the gene.

G S Watts, R O Pieper, J F Costello, Y M Peng, W S Dalton, B W Futscher

Open access · bronzeAbstract read
In one paragraph

Article in Molecular and cellular biology, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
72citing papers in PubMed, 1 pooled it
2.9field-weighted citation impact, top 8% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

72 citing papers in PubMed, 1 synthesis or guideline pooled it, 218 citations in OpenAlex.

  1. Pooled it
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  13. The Effects of OBalkan journal of medical genetics : BJMG · 2020
    Article
  14. Article
  15. A Review of Newly Diagnosed Glioblastoma.Frontiers in oncology · 2020
    Review
  16. Article
  17. OFrontiers in oncology · 2019
    Review
  18. Article
  19. Article
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12 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

6 authors at 4 institutions in 1 country.

G S WattsBone Marrow Transplant Program, Arizona Cancer Center, and Department of Pharmacology, University of Arizona, Tucson 85724, USA.
R O Pieper
J F Costello
Y M Peng
W S Dalton
B W Futscher
University of Arizona · USLoyola University Chicago · USLudwig Cancer Research · USUniversity of South Florida · US

Funding

Genomic Methylation--Mechanism to Alter Tumor PhenotypesR01CA065662 · NCI · UNIVERSITY OF ARIZONA · PI FUTSCHER, BERNARD W · 2001 to 2009
$2.3M
GENOMIC METHYLATION--A MECHANISM TO ALTER PHENOTYPESR29CA065662 · NCI · UNIVERSITY OF ARIZONA · PI FUTSCHER, BERNARD W · 1996 to 2000
$106k
MECHANISMS OF DRUG RESISTANCE IN MULTIPLE MYELOMAR01CA043043 · NCI · UNIVERSITY OF ARIZONA · PI DALTON, WILLIAM S. · 1992 to 1994
–
MECHANISMS OF DRUG RESISTANCE IN MULTIPLE MYELOMAR23CA043043 · NCI · UNIVERSITY OF ARIZONA · PI DALTON, WILLIAM S. · 1986 to 1986
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MECHANISMS OF DRUG RESISTANCE IN MULTIPLE MYELOMAR29CA043043 · NCI · UNIVERSITY OF ARIZONA · PI DALTON, WILLIAM S. · 1986 to 1990
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NCI NIH HHS CA43043NCI NIH HHS CA65662
6 · The paper itself

Abstract

O6-Methylguanine DNA methyltransferase (MGMT) repairs the mutagenic and cytotoxic O6-alkylguanine lesions produced by environmental carcinogens and the chemotherapeutic nitrosoureas. As such, MGMT-mediated repair of O6-alkylguanine lesions constitutes a major form of resistance to nitrosourea chemotherapy and makes control of MGMT expression of clinical interest. The variability of expression in cell lines and tissues, along with the ease with which the MGMT phenotype reverts under various conditions, suggests that MGMT is under epigenetic control. One such epigenetic mechanism, 5-methylation of cytosines, has been linked to MGMT expression. We have used an isogenic human multiple myeloma tumor cell line model composed of an MGMT-positive parent cell line, RPMI 8226/S, and its MGMT-negative variant, termed 8226/V, to study the control of MGMT expression. The loss of MGMT activity in 8226/V was found to be due to the loss of detectable MGMT gene expression. Bisulfite sequencing of the MGMT CpG island promoter revealed large increases in the levels of CpG methylation within discrete regions of the 8226/V MGMT CpG island compared to those in 8226/S. These changes in CpG methylation are associated with local heterochromatinization of the 8226/V MGMT transcription start site and provide a likely mechanism for the loss of MGMT transcription in 8226/V.

Indexed as

CpG IslandsDNA MethylationTranscription, GeneticCalcium Channel BlockersCells, CulturedChromatinCytosineDNA RepairGene ExpressionHumansMethyltransferasesO(6)-Methylguanine-DNA MethyltransferaseRestriction MappingVerapamilCalcium Channel BlockersChromatinCytosineMethyltransferasesO(6)-Methylguanine-DNA MethyltransferaseVerapamil

Identifiers

PMID9271436
PMCPMC232409
OpenAlexW1869160040

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.