Evidence map›Paper›PMID 41350447›Full record

ArticleCommunications medicine2025

Harnessing liquid biopsy to unveil RAS-MEK pathway somatic pathogenic variants in extracranial arterio-venous malformations.

Kartik D Bhatia, Dianne Sylvester, Bhavna Padhye, Caroline Bateman, David Lord, Geoffrey McCowage, Luciano Dalla-Pozza, Timothy Harrington, Brendan Steinfort, Mark Dexter and 3 more

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In one paragraph

Article in Communications medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Review
  2. Towards precision medicine for brain arteriovenous malformations.The Journal of clinical investigation · 2026
    Review
  3. 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

13 authors.

Kartik D BhatiaThe Children's Hospital at Westmead Clinical School, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW, Australia. kartik.bhatia@sydney.edu.au.ORCID http://orcid.org/0000-0002-3431-5647
Dianne SylvesterChildren's Cancer Research Unit, The Children's Hospital at Westmead, Westmead, NSW, Australia.ORCID http://orcid.org/0000-0002-9918-9266
Bhavna PadhyeThe Children's Hospital at Westmead Clinical School, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW, Australia.
Caroline BatemanChildren's Cancer Research Unit, The Children's Hospital at Westmead, Westmead, NSW, Australia.
David LordDepartment of Medical Imaging, The Children's Hospital at Westmead, Westmead, NSW, Australia.ORCID http://orcid.org/0000-0002-6468-4208
Geoffrey McCowageThe Children's Hospital at Westmead Clinical School, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW, Australia.
Luciano Dalla-PozzaThe Children's Hospital at Westmead Clinical School, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW, Australia.
Timothy HarringtonDepartment of Neurosurgery, Westmead Hospital, Westmead, NSW, Australia.
Brendan SteinfortDepartment of Neurosurgery, Westmead Hospital, Westmead, NSW, Australia.
Mark DexterDepartment of Neurosurgery, Westmead Hospital, Westmead, NSW, Australia.
Sarah Josephi-TaylorDepartment of Clinical Genetics, The Children's Hospital at Westmead, Westmead, NSW, Australia.
Russell DaleThe Children's Hospital at Westmead Clinical School, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW, Australia.ORCID http://orcid.org/0000-0002-2495-1826
Smadar Kahana-EdwinChildren's Cancer Research Unit, The Children's Hospital at Westmead, Westmead, NSW, Australia.ORCID http://orcid.org/0000-0002-2869-4310

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundArterio-venous malformations (AVMs) have been associated with somatic genetic variants in the RAS-MEK pathway, generating interest in the role of MEK inhibitors. However, open biopsy for molecular characterisation carries a potentially life-threatening bleeding risk.

methodsWe utilized liquid biopsy from the AVM efferent draining vein in 10 children and young adults (female 7, age range 7.3-22.2 years) with extracranial AVMs to identify the underlying somatic variants.

resultsHere we show identification of somatic mosaic variants in 8 of 10 patients. There were no procedural complications. Two patients with spinal arteriovenous metameric syndrome (Cobb syndrome) demonstrated somatic activating KRAS variants. Two additional patients had somatic in-frame deletion-insertion variants of HRAS. Three patients had other variants involving the RAS-MEK pathway and one within PIK3CA. Five patients have commenced molecularly directed pharmacotherapy leading to reduced disability. Variant allele frequency was inversely correlated with sampling distance from the nidus. One patient who underwent sampling at two separate embolization sessions demonstrated a higher variant allele frequency in the sample obtained after embolization was completed.

conclusionsOur study further supports the role of the RAS-MEK pathway in AVM pathophysiology. In addition, we demonstrate the effective use of liquid biopsy to genotype extracranial AVMs in children. Finally, we provide insights into how the localized high-pressure high-flow conditions within the AVM distinctly shape cell free DNA fragmentation patterns.

Identifiers

PMID41350447
PMCPMC12680647

What Socratic holds

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LicenceCC BY
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Registered trials

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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 Socratic graph.