Evidence map›Paper›PMID 37436963›Full record

ArticleNeuro-oncology2023

Novel SOX10 indel mutations drive schwannomas through impaired transactivation of myelination gene programs.

Erik A Williams, Ajay Ravindranathan, Rohit Gupta, Nicholas O Stevers, Abigail K Suwala, Chibo Hong, Somang Kim, Jimmy Bo Yuan, Jasper Wu, Jairo Barreto and 31 more

Open access · hybridAbstract read
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In one paragraph

Article in Neuro-oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
5.8field-weighted citation impact, top 3% 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

24 citing papers in PubMed, 28 citations in OpenAlex.

  1. TANC1::HTRA1 fusion in schwannomas.Brain pathology (Zurich, Switzerland) · 2026
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  6. A Genomically Tailored Multiagent Precision Medicine Clinical Trial for Adults with Recurrent Glioblastoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
    Article
  7. Article
  8. Review
  9. Review
  10. Beyond Hybrid Morphology: A Large Series of Fusion-Driven Benign Peripheral Nerve Sheath Tumors Including 5 Tumors With Novel Fusions.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2025
    Article
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  12. Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

41 authors at 11 institutions in 2 countries.

Erik A WilliamsDepartment of Pathology, University of California, San Francisco, San Francisco, California, USA.ORCID 0000-0002-9190-2450
Ajay RavindranathanDepartment of Pathology, University of California, San Francisco, San Francisco, California, USA.
Rohit GuptaDepartment of Pathology, University of California, San Francisco, San Francisco, California, USA.
Nicholas O SteversDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.ORCID 0000-0003-1082-6423
Abigail K SuwalaDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.
Chibo HongDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.
Somang KimDepartment of Physics and Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
Jimmy Bo YuanDepartment of Physics and Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
Jasper WuDepartment of Pathology, University of California, San Francisco, San Francisco, California, USA.
Jairo BarretoDepartment of Pathology, University of California, San Francisco, San Francisco, California, USA.
Calixto-Hope G LucasDepartment of Pathology, University of California, San Francisco, San Francisco, California, USA.
Emily ChanDepartment of Pathology, University of California, San Francisco, San Francisco, California, USA.
Melike PekmezciDepartment of Pathology, University of California, San Francisco, San Francisco, California, USA.
Philip E LeBoitDepartment of Pathology, University of California, San Francisco, San Francisco, California, USA.
Thaddeus MullyDepartment of Pathology, University of California, San Francisco, San Francisco, California, USA.
Arie PerryDepartment of Pathology, University of California, San Francisco, San Francisco, California, USA.
Andrew BollenDepartment of Pathology, University of California, San Francisco, San Francisco, California, USA.
Jessica Van ZiffleDepartment of Pathology, University of California, San Francisco, San Francisco, California, USA.
W Patrick DevineDepartment of Pathology, University of California, San Francisco, San Francisco, California, USA.
Alyssa T ReddyDepartments of Neurology and Pediatrics, University of California, San Francisco, San Francisco, California, USA.
Nalin GuptaDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.ORCID 0000-0001-9539-7052
Kristen M BasnetVista Pathology Laboratory, Medford, Oregon, USA.
Robert J B MacaulayDepartment of Pathology, Moffitt Cancer Center, Tampa, Florida, USA.
Patrick MalafronteDepartment of Pathology, Tampa General Hospital, Tampa, Florida, USA.
Han LeeDepartment of Pathology, University of California, Davis, Sacramento, California, USA.
William H YongDepartment of Pathology and Laboratory Medicine, University of California, Irvine, Irvine, California, USA.
Kevin Jon WilliamsDepartments of Physiology and Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania, USA.
Tareq A JuratliDepartment of Neurosurgery, Division of Neuro-Oncology, Faculty of Medicine and Carl Gustav Carus University Hospital, Dresden, Germany.
Douglas A MataFoundation Medicine, Inc., Cambridge, Massachusetts, USA.
Richard S P HuangFoundation Medicine, Inc., Cambridge, Massachusetts, USA.
Matthew C HiemenzFoundation Medicine, Inc., Cambridge, Massachusetts, USA.
Dean C PavlickFoundation Medicine, Inc., Cambridge, Massachusetts, USA.
Garrett M FramptonFoundation Medicine, Inc., Cambridge, Massachusetts, USA.
Tyler JanovitzFoundation Medicine, Inc., Cambridge, Massachusetts, USA.
Jeffrey S RossFoundation Medicine, Inc., Cambridge, Massachusetts, USA.
Susan M ChangDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.
Mitchel S BergerDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.
Line JacquesDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.ORCID 0000-0002-2691-587X
Jun S SongDepartment of Physics and Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.ORCID 0000-0002-0422-2175
Joseph F CostelloDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.ORCID 0000-0003-3189-584X
David A SolomonDepartment of Pathology, University of California, San Francisco, San Francisco, California, USA.ORCID 0000-0003-4571-7999
University of California, San Francisco · USFoundation Medicine (United States)University of Illinois Urbana-Champaign · USMedford Radiology Group · USMoffitt Cancer Center · USSUNY Upstate Medical University · USTampa General Hospital · USTemple University · USUniversity Hospital Carl Gustav Carus · DEUniversity of California, Davis · USUniversity of California, Irvine · US

Funding

Univ.of Calif., Irvine Cancer Center Support GrantP30CA062203 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI Melanie Funes · 1994 to 2026
$57.9M
Tissue CoreP50CA097257 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Susan M Chang · 2002 to 2026
$57.4M
Predicting Transcriptional and Epigenetic Networks in Cancer from Sequencing DataR01CA163336 · NCI · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI Jun S Song · 2012 to 2026
$4.4M
The Immortality and Evolution of Adult Brain TumorsR50CA274229 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Chibo Hong · 2022 to 2026
$899k
Identification of a GABP Feedback Loop and its Role in Tumor Cell ImmortalityF31CA254067 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI STEVERS, NICHOLAS OLIVER · 2020 to 2022
$125k
NCI NIH HHS F31 CA254067NCI NIH HHS P30 CA062203NCI NIH HHS P50 CA097257NCI NIH HHS R01 CA163336NCI NIH HHS R50 CA274229
6 · The paper itself

Abstract

backgroundSchwannomas are common peripheral nerve sheath tumors that can cause severe morbidity given their stereotypic intracranial and paraspinal locations. Similar to many solid tumors, schwannomas and other nerve sheath tumors are primarily thought to arise due to aberrant hyperactivation of the RAS growth factor signaling pathway. Here, we sought to further define the molecular pathogenesis of schwannomas.

methodsWe performed comprehensive genomic profiling on a cohort of 96 human schwannomas, as well as DNA methylation profiling on a subset. Functional studies including RNA sequencing, chromatin immunoprecipitation-DNA sequencing, electrophoretic mobility shift assay, and luciferase reporter assays were performed in a fetal glial cell model following transduction with wildtype and tumor-derived mutant isoforms of SOX10.

resultsWe identified that nearly one-third of sporadic schwannomas lack alterations in known nerve sheath tumor genes and instead harbor novel recurrent in-frame insertion/deletion mutations in SOX10, which encodes a transcription factor responsible for controlling Schwann cell differentiation and myelination. SOX10 indel mutations were highly enriched in schwannomas arising from nonvestibular cranial nerves (eg facial, trigeminal, vagus) and were absent from vestibular nerve schwannomas driven by NF2 mutation. Functional studies revealed these SOX10 indel mutations have retained DNA binding capacity but impaired transactivation of glial differentiation and myelination gene programs.

conclusionsWe thus speculate that SOX10 indel mutations drive a unique subtype of schwannomas by impeding proper differentiation of immature Schwann cells.

Indexed as

Nerve Sheath NeoplasmsNeurilemmomaNeuroma, AcousticHumansINDEL MutationMutationSOXE Transcription FactorsTranscriptional ActivationSOX10 protein, humanSOXE Transcription FactorsmyelinationPMP2Schwann cellschwannomaSOX10

Identifiers

PMID37436963
PMCPMC10708934
OpenAlexW4383997413

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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.