Evidence map›Paper›PMID 34729487›Full record

ArticleNeuro-oncology advances

Intraoperative DNA methylation classification of brain tumors impacts neurosurgical strategy.

Luna Djirackor, Skarphedinn Halldorsson, Pitt Niehusmann, Henning Leske, David Capper, Luis P Kuschel, Jens Pahnke, Bernt J Due-Tønnessen, Iver A Langmoen, Cecilie J Sandberg and 2 more

Open access · goldAbstract read
In one paragraph

Article in Neuro-oncology advances. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
66citing papers in PubMed, 1 pooled it
7.8field-weighted citation impact, top 2% 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, 1 synthesis or guideline pooled it, 83 citations in OpenAlex.

  1. Pooled it
  2. A multi-analyte blood test for acute spinal cord injury.The Journal of clinical investigation · 2025
    Trial
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  6. The emerging role of intraoperative nanopore sequencing on the neurosurgical strategy in paediatric embryonal brain tumours.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2026
    Review
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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

12 authors at 3 institutions in 3 countries.

Luna DjirackorInstitute for Surgical Research/Department of Neurosurgery, Vilhelm Magnus Laboratory for Neurosurgical Research, Oslo University Hospital, Oslo, Norway.
Skarphedinn HalldorssonInstitute for Surgical Research/Department of Neurosurgery, Vilhelm Magnus Laboratory for Neurosurgical Research, Oslo University Hospital, Oslo, Norway.ORCID https://orcid.org/0000-0003-4337-9252
Pitt NiehusmannSection of Neuropathology, Department of Pathology, Oslo University Hospital, Oslo, Norway.
Henning LeskeSection of Neuropathology, Department of Pathology, Oslo University Hospital, Oslo, Norway.
David CapperDepartment of Neuropathology, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Luis P KuschelDepartment of Neurology, Charité-Universitätsmedizin Berlin, Berlin,Germany.
Jens PahnkeSection of Neuropathology, Department of Pathology, Oslo University Hospital, Oslo, Norway.
Bernt J Due-TønnessenDepartment of Neurosurgery, Oslo University Hospital, Oslo, Norway.
Iver A LangmoenInstitute for Surgical Research/Department of Neurosurgery, Vilhelm Magnus Laboratory for Neurosurgical Research, Oslo University Hospital, Oslo, Norway.
Cecilie J SandbergInstitute for Surgical Research/Department of Neurosurgery, Vilhelm Magnus Laboratory for Neurosurgical Research, Oslo University Hospital, Oslo, Norway.
Philipp EuskirchenGerman Cancer Consortium (DKTK), Partner Site Berlin, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Einar O Vik-MoInstitute for Surgical Research/Department of Neurosurgery, Vilhelm Magnus Laboratory for Neurosurgical Research, Oslo University Hospital, Oslo, Norway.
Oslo University Hospital · NOGerman Cancer Research Center · DECharité - Universitätsmedizin Berlin · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundBrain tumor surgery must balance the benefit of maximal resection against the risk of inflicting severe damage. The impact of increased resection is diagnosis-specific. However, the precise diagnosis is typically uncertain at surgery due to limitations of imaging and intraoperative histomorphological methods. Novel and accurate strategies for brain tumor classification are necessary to support personalized intraoperative neurosurgical treatment decisions. Here, we describe a fast and cost-efficient workflow for intraoperative classification of brain tumors based on DNA methylation profiles generated by low coverage nanopore sequencing and machine learning algorithms.

methodsWe evaluated 6 independent cohorts containing 105 patients, including 50 pediatric and 55 adult patients. Ultra-low coverage whole-genome sequencing was performed on nanopore flow cells. Data were analyzed using copy number variation and ad hoc random forest classifier for the genome-wide methylation-based classification of the tumor.

resultsConcordant classification was obtained between nanopore DNA methylation analysis and a full neuropathological evaluation in 93 of 105 (89%) cases. The analysis demonstrated correct diagnosis in 6/6 cases where frozen section evaluation was inconclusive. Results could be returned to the operating room at a median of 97 min (range 91-161 min). Precise classification of the tumor entity and subtype would have supported modification of the surgical strategy in 12 out of 20 patients evaluated intraoperatively.

conclusionIntraoperative nanopore sequencing combined with machine learning diagnostics was robust, sensitive, and rapid. This strategy allowed DNA methylation-based classification of the tumor to be returned to the surgeon within a timeframe that supports intraoperative decision making.

Indexed as

brain tumorDNA methylationextent of resectionintraoperative diagnosticsnanopore

Identifiers

PMID34729487
PMCPMC8557693
OpenAlexW3207346302

What OpenQuestion holds

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LicenceCC BY-NC
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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.