Evidence map›Paper›PMID 25910840›Full record

ArticleNeuro-oncology2015

The MGMT promoter SNP rs16906252 is a risk factor for MGMT methylation in glioblastoma and is predictive of response to temozolomide.

Robert W Rapkins, Fan Wang, HuyTram N Nguyen, Timothy F Cloughesy, Albert Lai, Wendy Ha, Anna K Nowak, Megan P Hitchins, Kerrie L McDonald

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuro-oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed, 2 pooled it
5.2field-weighted citation impact, top 4% 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

36 citing papers in PubMed, 2 syntheses or guidelines pooled it, 68 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Article
  4. Article
  5. Review
  6. Article
  7. Association ofCancers · 2023
    Article
  8. Pharmaceuticals (Basel, Switzerland) · 2023
    Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Cancers · 2021
    Review
  14. Deciphering the genetic code of DNA methylation.Briefings in bioinformatics · 2021
    Review
  15. Article
  16. Article
  17. Observational
  18. Article
  19. Article
  20. Review
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

9 authors at 3 institutions in 3 countries.

Robert W RapkinsCure Brain Cancer Neuro-oncology Laboratory, Prince of Wales Clinical School, Lowy Cancer Research Centre, University of New South Wales, Sydney, Australia (R.W.R., W.H., K.L.M.); Department of Medicine (Oncology), Stanford Cancer Institute, Stanford University, Stanford, California (F.W., M.P.H.); School of Public Health, Harbin Medical University, Harbin, People's Republic of China (F.W.); Department of Neurology, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, California (H.N.N., T.F.C., A.L.); School of Medicine and Pharmacology, University of Western Australia, Perth, Australia (A.N.).
Fan WangCure Brain Cancer Neuro-oncology Laboratory, Prince of Wales Clinical School, Lowy Cancer Research Centre, University of New South Wales, Sydney, Australia (R.W.R., W.H., K.L.M.); Department of Medicine (Oncology), Stanford Cancer Institute, Stanford University, Stanford, California (F.W., M.P.H.); School of Public Health, Harbin Medical University, Harbin, People's Republic of China (F.W.); Department of Neurology, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, California (H.N.N., T.F.C., A.L.); School of Medicine and Pharmacology, University of Western Australia, Perth, Australia (A.N.).
HuyTram N NguyenCure Brain Cancer Neuro-oncology Laboratory, Prince of Wales Clinical School, Lowy Cancer Research Centre, University of New South Wales, Sydney, Australia (R.W.R., W.H., K.L.M.); Department of Medicine (Oncology), Stanford Cancer Institute, Stanford University, Stanford, California (F.W., M.P.H.); School of Public Health, Harbin Medical University, Harbin, People's Republic of China (F.W.); Department of Neurology, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, California (H.N.N., T.F.C., A.L.); School of Medicine and Pharmacology, University of Western Australia, Perth, Australia (A.N.).
Timothy F CloughesyCure Brain Cancer Neuro-oncology Laboratory, Prince of Wales Clinical School, Lowy Cancer Research Centre, University of New South Wales, Sydney, Australia (R.W.R., W.H., K.L.M.); Department of Medicine (Oncology), Stanford Cancer Institute, Stanford University, Stanford, California (F.W., M.P.H.); School of Public Health, Harbin Medical University, Harbin, People's Republic of China (F.W.); Department of Neurology, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, California (H.N.N., T.F.C., A.L.); School of Medicine and Pharmacology, University of Western Australia, Perth, Australia (A.N.).
Albert LaiCure Brain Cancer Neuro-oncology Laboratory, Prince of Wales Clinical School, Lowy Cancer Research Centre, University of New South Wales, Sydney, Australia (R.W.R., W.H., K.L.M.); Department of Medicine (Oncology), Stanford Cancer Institute, Stanford University, Stanford, California (F.W., M.P.H.); School of Public Health, Harbin Medical University, Harbin, People's Republic of China (F.W.); Department of Neurology, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, California (H.N.N., T.F.C., A.L.); School of Medicine and Pharmacology, University of Western Australia, Perth, Australia (A.N.).
Wendy HaCure Brain Cancer Neuro-oncology Laboratory, Prince of Wales Clinical School, Lowy Cancer Research Centre, University of New South Wales, Sydney, Australia (R.W.R., W.H., K.L.M.); Department of Medicine (Oncology), Stanford Cancer Institute, Stanford University, Stanford, California (F.W., M.P.H.); School of Public Health, Harbin Medical University, Harbin, People's Republic of China (F.W.); Department of Neurology, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, California (H.N.N., T.F.C., A.L.); School of Medicine and Pharmacology, University of Western Australia, Perth, Australia (A.N.).
Anna K NowakCure Brain Cancer Neuro-oncology Laboratory, Prince of Wales Clinical School, Lowy Cancer Research Centre, University of New South Wales, Sydney, Australia (R.W.R., W.H., K.L.M.); Department of Medicine (Oncology), Stanford Cancer Institute, Stanford University, Stanford, California (F.W., M.P.H.); School of Public Health, Harbin Medical University, Harbin, People's Republic of China (F.W.); Department of Neurology, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, California (H.N.N., T.F.C., A.L.); School of Medicine and Pharmacology, University of Western Australia, Perth, Australia (A.N.).
Megan P HitchinsCure Brain Cancer Neuro-oncology Laboratory, Prince of Wales Clinical School, Lowy Cancer Research Centre, University of New South Wales, Sydney, Australia (R.W.R., W.H., K.L.M.); Department of Medicine (Oncology), Stanford Cancer Institute, Stanford University, Stanford, California (F.W., M.P.H.); School of Public Health, Harbin Medical University, Harbin, People's Republic of China (F.W.); Department of Neurology, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, California (H.N.N., T.F.C., A.L.); School of Medicine and Pharmacology, University of Western Australia, Perth, Australia (A.N.).
Kerrie L McDonaldCure Brain Cancer Neuro-oncology Laboratory, Prince of Wales Clinical School, Lowy Cancer Research Centre, University of New South Wales, Sydney, Australia (R.W.R., W.H., K.L.M.); Department of Medicine (Oncology), Stanford Cancer Institute, Stanford University, Stanford, California (F.W., M.P.H.); School of Public Health, Harbin Medical University, Harbin, People's Republic of China (F.W.); Department of Neurology, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, California (H.N.N., T.F.C., A.L.); School of Medicine and Pharmacology, University of Western Australia, Perth, Australia (A.N.).
Stanford University · USUNSW Sydney · AUUniversity of California, Los Angeles · US

Funding

Investigation of tumor suppressive miR-148a in IDH mutant gliomasR01CA179071 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LAI, ALBERT · 2014 to 2018
$1.6M
NCI NIH HHS R01 CA179071
6 · The paper itself

Abstract

backgroundPromoter methylation of O(6)-methylguanine-DNA methyltransferase (MGMT) is an important predictive biomarker in glioblastoma. The T variant of the MGMT promoter-enhancer single nucleotide polymorphism (SNP; rs16906252) has been associated with the presence of MGMT promoter methylation in other cancers. We examined the association of the T allele of rs16906252 with glioblastoma development, tumor MGMT methylation, MGMT protein expression, and survival outcomes.

methodsTwo independent temozolomide-treated glioblastoma cohorts-one Australian (Australian Genomics and Clinical Outcomes of Glioma, n = 163) and the other American (University of California Los Angeles/Kaiser Permanente Los Angeles, n = 159)-were studied. Allelic bisulphite sequencing was used to determine if methylation was specific to the T allele. Additionally, we compared the incidence of the T allele between glioblastoma cases and matched controls to assess whether it was a risk factor for developing MGMT methylated glioblastoma.

resultsCarriage of the T allele of the rs16906252 SNP was associated with both MGMT methylation and low MGMT protein expression and predicted significantly longer survival in temozolomide-treated patients with both MGMT methylated and nonmethylated glioblastoma. Methylation was linked to the T allele, inferring that the T variant plays a key role in the acquisition of MGMT methylation. Carriage of the T allele was associated with a significantly elevated risk of developing glioblastoma (adjusted odds ratio, 1.96; P = .013), increasing further when glioblastoma was classified by the presence of MGMT methylation (adjusted odds ratio, 2.86; P = .001).

conclusionsThe T allele of the rs16906252 SNP is a key determinant in the acquisition of MGMT methylation in glioblastoma. Temozolomide-treated patients with the rs16906252 T genotype have better survival, irrespective of tumor methylation status.

Indexed as

Polymorphism, Single NucleotideAdultAgedAged, 80 and overAllelesAntineoplastic Agents, AlkylatingBiomarkersBrain NeoplasmsDacarbazineDNA Modification MethylasesDNA Repair EnzymesFemaleGenotypeGlioblastomaHumansKaplan-Meier EstimateAntineoplastic Agents, AlkylatingBiomarkersDacarbazineDNA Modification MethylasesDNA Repair EnzymesMGMT protein, humanTemozolomideTumor Suppressor ProteinsMGMT methylationSNPsurvival

Identifiers

PMID25910840
PMCPMC4633927
OpenAlexW2112170577

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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.