Evidence map›Paper›PMID 26940435›Full record

ArticleScientific reports2016

Intratumoral heterogeneity identified at the epigenetic, genetic and transcriptional level in glioblastoma.

Nicole R Parker, Amanda L Hudson, Peter Khong, Jonathon F Parkinson, Trisha Dwight, Rowan J Ikin, Ying Zhu, Zhangkai Jason Cheng, Fatemeh Vafaee, Jason Chen and 2 more

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

Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 111 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
111citing papers in PubMed, 2 pooled it
13.1field-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.

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

111 citing papers in PubMed, 2 syntheses or guidelines pooled it, 165 citations in OpenAlex.

  1. Pooled it
  2. Anti-epidermal growth factor receptor therapy for glioblastoma in adults.The Cochrane database of systematic reviews · 2020
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51 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

12 authors at 2 institutions in 1 country.

Nicole R ParkerSydney Neuro-Oncology Group, Bill Walsh Translational Cancer Research Laboratory, Kolling Institute, St Leonards, NSW, Australia, 2065.
Amanda L HudsonSydney Neuro-Oncology Group, Bill Walsh Translational Cancer Research Laboratory, Kolling Institute, St Leonards, NSW, Australia, 2065.
Peter KhongSydney Neuro-Oncology Group, Bill Walsh Translational Cancer Research Laboratory, Kolling Institute, St Leonards, NSW, Australia, 2065.
Jonathon F ParkinsonSydney Neuro-Oncology Group, Bill Walsh Translational Cancer Research Laboratory, Kolling Institute, St Leonards, NSW, Australia, 2065.
Trisha DwightCancer Genetics, Hormones and Cancer Group, Kolling Institute, St Leonards, Australia, 2065.
Rowan J IkinSydney Neuro-Oncology Group, Bill Walsh Translational Cancer Research Laboratory, Kolling Institute, St Leonards, NSW, Australia, 2065.
Ying ZhuNorthern Sydney Local Health District, St Leonards, NSW, Australia, 2065.
Zhangkai Jason ChengDepartment of Physics, University of Sydney, NSW, Australia, 2006.
Fatemeh VafaeeCharles Perkins Centre, University of Sydney, NSW, Australia, 2006.
Jason ChenDepartment of Anatomical Pathology, Northern Sydney Local Health District, St Leonards, NSW, Australia, 2065.
Helen R WheelerSydney Neuro-Oncology Group, Bill Walsh Translational Cancer Research Laboratory, Kolling Institute, St Leonards, NSW, Australia, 2065.
Viive M HowellSydney Neuro-Oncology Group, Bill Walsh Translational Cancer Research Laboratory, Kolling Institute, St Leonards, NSW, Australia, 2065.
Northern Sydney Local Health District · AUUniversity of Sydney · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Heterogeneity is a hallmark of glioblastoma with intratumoral heterogeneity contributing to variability in responses and resistance to standard treatments. Promoter methylation status of the DNA repair enzyme O(6)-methylguanine DNA methyltransferase (MGMT) is the most important clinical biomarker in glioblastoma, predicting for therapeutic response. However, it does not always correlate with response. This may be due to intratumoral heterogeneity, with a single biopsy unlikely to represent the entire lesion. Aberrations in other DNA repair mechanisms may also contribute. This study investigated intratumoral heterogeneity in multiple glioblastoma tumors with a particular focus on the DNA repair pathways. Transcriptional intratumoral heterogeneity was identified in 40% of cases with variability in MGMT methylation status found in 14% of cases. As well as identifying intratumoral heterogeneity at the transcriptional and epigenetic levels, targeted next generation sequencing identified between 1 and 37 unique sequence variants per specimen. In-silico tools were then able to identify deleterious variants in both the base excision repair and the mismatch repair pathways that may contribute to therapeutic response. As these pathways have roles in temozolomide response, these findings may confound patient management and highlight the importance of assessing multiple tumor biopsies.

Indexed as

AdultAgedAged, 80 and overAntineoplastic Agents, AlkylatingBiomarkers, PharmacologicalBiomarkers, TumorBiopsyBrain NeoplasmsDacarbazineDNA MethylationDNA Modification MethylasesDNA Repair EnzymesFemaleFollow-Up StudiesGene Expression ProfilingGlioblastomaAntineoplastic Agents, AlkylatingBiomarkers, PharmacologicalBiomarkers, TumorDacarbazineDNA Modification MethylasesDNA Repair EnzymesMGMT protein, humanTemozolomideTumor Suppressor Proteins

Identifiers

PMID26940435
PMCPMC4778014
OpenAlexW2302258827

What OpenQuestion holds

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LicenceCC BY
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.