Evidence map›Paper›PMID 27577993›Full record

ArticleActa neuropathologica communications2016

Targeted detection of genetic alterations reveal the prognostic impact of H3K27M and MAPK pathway aberrations in paediatric thalamic glioma.

Scott Ryall, Rahul Krishnatry, Anthony Arnoldo, Pawel Buczkowicz, Matthew Mistry, Robert Siddaway, Cino Ling, Sanja Pajovic, Man Yu, Joshua B Rubin and 6 more

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

Article in Acta neuropathologica communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed, 2 pooled it
9.3field-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

63 citing papers in PubMed, 2 syntheses or guidelines pooled it, 120 citations in OpenAlex.

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  9. Molecular-targeted therapy for childhood low-grade glial and glioneuronal tumors.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2024
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3 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 4 institutions in 3 countries.

Scott RyallArthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, ON, Canada.ORCID 0000-0002-5327-3892
Rahul KrishnatryArthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, ON, Canada.
Anthony ArnoldoDivision of Pathology, Hospital for Sick Children, Toronto, ON, Canada.
Pawel BuczkowiczArthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, ON, Canada.
Matthew MistryArthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, ON, Canada.
Robert SiddawayArthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, ON, Canada.
Cino LingArthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, ON, Canada.
Sanja PajovicArthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, ON, Canada.
Man YuArthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, ON, Canada.
Joshua B RubinDepartment of Paediatrics, Washington University School of Medicine in St. Louis, St. Louis, MO, USA.
Juliette HukinDivision of Neurology and Oncology, Department of Paediatrics, University of British Columbia & British Columbia Children's Hospital, Vancouver, BC, Canada.
Paul SteinbokDivision of Paediatric Neurosurgery, Department of Surgery, University of British Columbia & British Columbia Children's Hospital, Vancouver, BC, Canada.
Ute BartelsDivision of Haematology/Oncology, Hospital for Sick Children, Toronto, ON, Canada.
Eric BouffetDivision of Haematology/Oncology, Hospital for Sick Children, Toronto, ON, Canada.
Uri TaboriArthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, ON, Canada.
Cynthia HawkinsArthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, ON, Canada. cynthia.hawkins@sickkids.ca.
Hospital for Sick Children · CAUniversity of British Columbia · CAUniversity of Toronto · CAWashington University in St. Louis · US

Funding

CIHR
6 · The paper itself

Abstract

Paediatric brain tumours arising in the thalamus present significant diagnostic and therapeutic challenges to physicians due to their sensitive midline location. As such, genetic analysis for biomarkers to aid in the diagnosis, prognosis and treatment of these tumours is needed. Here, we identified 64 thalamic gliomas with clinical follow-up and characterized targeted genomic alterations using newly optimized droplet digital and NanoString-based assays. The median age at diagnosis was 9.25 years (range, 0.63-17.55) and median survival was 6.43 (range, 0.01-27.63) years. Our cohort contained 42 and 22 tumours reviewed as low and high grade gliomas, respectively. Five (12 %) low grade and 11 (50 %) high grade gliomas were positive for the H3F3A/HIST1H3B K27M (H3K27M) mutation. Kaplan-Meier survival analysis revealed significantly worse overall survival for patients harbouring the H3K27M mutation versus H3F3A/HIST1H3B wild type (H3WT) samples (log-rank p < 0.0001) with a median survival of 1.02 vs. 9.12 years. Mitogen-activated protein kinase (MAPK) pathway activation via BRAF or FGFR1 hotspot mutations or fusion events were detected in 44 % of patients, and was associated with long-term survival in the absence of H3K27M (log-rank p < 0.0001). Multivariate analysis demonstrated H3K27M status and high grade histology to be the most significant independent predictors of poor overall survival with hazard ratios of 6.945 and 7.721 (p < 0.0001), respectively. In contrast, MAPK pathway activation is a predictor of favourable patient outcome, although not independent of other clinical factors. Importantly, we show that low grade malignancies may harbour H3K27M mutations and that these tumours show a dismal survival compared to low grade H3WT cases. Our data strongly supports the inclusion of targeted genetic testing in childhood thalamic tumours to most accurately stratify patients into appropriate risk groups.

Indexed as

ThalamusAdolescentBiomarkers, TumorBrain NeoplasmsChildChild, PreschoolFemaleFollow-Up StudiesGliomaHumansInfantKaplan-Meier EstimateMaleMAP Kinase Signaling SystemMultivariate AnalysisMutationBiomarkers, TumorBRAFH3K27MMAPKPediatricPrognosticThalamic glioma

Identifiers

PMID27577993
PMCPMC5006436
OpenAlexW2507778697

What OpenQuestion holds

Textmetadata
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.