Evidence map›Paper›PMID 27571882›Full record

ArticleNeuro-oncology2017

Human TERT promoter mutation enables survival advantage from MGMT promoter methylation in IDH1 wild-type primary glioblastoma treated by standard chemoradiotherapy.

HuyTram N Nguyen, Amy Lie, Tie Li, Reshmi Chowdhury, Fei Liu, Byram Ozer, Bowen Wei, Richard M Green, Benjamin M Ellingson, He-Jing Wang and 6 more

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

Article in Neuro-oncology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
66citing papers in PubMed, 3 pooled it
5.4field-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

66 citing papers in PubMed, 3 syntheses or guidelines pooled it, 80 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
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6 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

16 authors at 2 institutions in 1 country.

HuyTram N NguyenDepartment of Neurology, David Geffen School of Medicine at UCLA, University of California, Los Angeles, California, USA.
Amy LieDepartment of Neurology, David Geffen School of Medicine at UCLA, University of California, Los Angeles, California, USA.
Tie LiDepartment of Neurology, David Geffen School of Medicine at UCLA, University of California, Los Angeles, California, USA.
Reshmi ChowdhuryDepartment of Neurology, David Geffen School of Medicine at UCLA, University of California, Los Angeles, California, USA.
Fei LiuDepartment of Neurology, David Geffen School of Medicine at UCLA, University of California, Los Angeles, California, USA.
Byram OzerDepartment of Neurology, David Geffen School of Medicine at UCLA, University of California, Los Angeles, California, USA.
Bowen WeiDepartment of Pathology, David Geffen School of Medicine at UCLA, University of California, Los Angeles, California, USA.
Richard M GreenKaiser Permanente Southern California, Los Angeles, California, USA.
Benjamin M EllingsonDepartment of Radiological Sciences, David Geffen School of Medicine at UCLA, University of California, Los Angeles, California, USA.
He-Jing WangDepartment of Biomathematics, David Geffen School of Medicine at UCLA, University of California, Los Angeles, California, USA.
Robert ElashoffDepartment of Biomathematics, David Geffen School of Medicine at UCLA, University of California, Los Angeles, California, USA.
Linda M LiauDepartment of Neurosurgery, David Geffen School of Medicine at UCLA, University of California, Los Angeles, California, USA.
William H YongDepartment of Pathology, David Geffen School of Medicine at UCLA, University of California, Los Angeles, California, USA.
Phioanh L NghiemphuDepartment of Neurology, David Geffen School of Medicine at UCLA, University of California, Los Angeles, California, USA.
Timothy CloughesyDepartment of Neurology, David Geffen School of Medicine at UCLA, University of California, Los Angeles, California, USA.
Albert LaiDepartment of Neurology, David Geffen School of Medicine at UCLA, University of California, Los Angeles, California, USA.
Kaiser Permanente · USUniversity 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

Background: Promoter mutation in the human telomerase reverse transcriptase gene (hTERT) occurs in ~75% of primary glioblastoma (GBM). Although the mutation appears to upregulate telomerase expression and contributes to the maintenance of telomere length, its clinical significance remains unclear. Methods: We performed hTERT promoter genotyping on 303 isocitrate dehydrogenase 1 wild-type GBM tumors treated with standard chemoradiotherapy. We also stratified 190 GBM patients from the database of The Cancer Genome Atlas (TCGA) by hTERT gene expression. We analyzed overall and progression-free survival by Kaplan-Meier and Cox regression. Results: We detected hTERT promoter mutation in 75% of the patients. When included as the only biomarker, hTERT mutation was not prognostic in our patient cohort by Cox regression analysis. However, when hTERT and O6-DNA methylguanine-methyltransferase (MGMT) were included together, we observed an interaction between these 2 factors. To further investigate this interaction, we performed pairwise comparison of the 4 patient subcohorts grouped by hTERT-MGMT status (MUT-M, WT-M, MUT-U, and WT-U). MGMT methylated patients showed improved survival only in the presence of hTERT promoter mutation: MUT-M versus MUT-U (overall survival of 28.3 vs 15.9 mos, log-rank P < .0001 and progression-free survival of 15.4 vs 7.86 mo, log-rank P < .0001). These results were confirmed by Cox analyses. Analogously, the cohort from TCGA demonstrated survival benefit of MGMT promoter methylation only in patients with high hTERT expression. In addition, hTERT mutation was negatively prognostic in our MGMT unmethylated patients, while the analogous association with high expression was not observed in the cohort from TCGA. Conclusion: The prognostic influence of MGMT promoter methylation depends on hTERT promoter mutation. This interaction warrants further mechanistic investigation.

Indexed as

DNA MethylationAgedBiomarkers, TumorBrain NeoplasmsChemoradiotherapyDNA Modification MethylasesDNA Repair EnzymesFemaleGlioblastomaHumansIsocitrate DehydrogenaseMaleMiddle AgedMutationNeoplasm GradingNeoplasm Recurrence, LocalBiomarkers, TumorDNA Modification MethylasesDNA Repair EnzymesIDH1 protein, humanIsocitrate DehydrogenaseMGMT protein, humanTelomeraseTERT protein, humanTumor Suppressor ProteinshTERT promoter mutationMGMT promoter methylationoverall survivalprimary glioblastomaprogression free survival

Identifiers

PMID27571882
PMCPMC5464302
OpenAlexW2514238202

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.