Evidence map›Paper›PMID 41784910›Full record

ArticleJournal of neuro-oncology2026

PTPN11-related Noonan syndrome predisposes to multifocal low-grade CNS tumors harboring FGFR1 variants.

Gary Kohanbash, Scott Ryall, Sam E Gary, Lindsey M Hoffman, Robert Siddaway, Anne E Bendel, Karen W Gripp, Andrew W Walter, Jordan R Hansford, Amy A Smith and 5 more

Abstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of neuro-oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors.

Gary KohanbashDepartment of Neurological Surgery, University of Pittsburgh, Pittsburgh, PA, USA. gary.kohanbash@pitt.edu.
Scott RyallThe Arthur and Sonia Labatt Brain Tumour Research Center, The Hospital for Sick Children, Toronto, ON, Canada.
Sam E GaryDepartment of Neurological Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
Lindsey M HoffmanDivision of Hematology-Oncology, Children's Hospital of Colorado, Aurora, CO, USA.
Robert SiddawayDivision of Pathology, Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, ON, Canada.
Anne E BendelDivision of Hematology-Oncology, Children's Minnesota, Minneapolis, MN, USA.
Karen W GrippDivision of Medical Genetics, Nemours Children's Health, Wilmington, DE, USA.
Andrew W WalterDivision of Hematology-Oncology, Nemours Children's Health, Wilmington, DE, USA.
Jordan R HansfordChildren's Cancer Centre, Royal Children's Hospital, Melbourne, Australia.
Amy A SmithDivision of Pediatric Hematology-Oncology, Arnold Palmer Hospital, Orlando, FL, USA.
Hong WangSchool of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
John M SkaugenDepartment of Pathology, University of Pittsburgh, Pittsburgh, PA, USA.
Uri TaboriDivision of Pediatric Hematology-Oncology, Department of Pediatrics, The Hospital for Sick Children, Toronto, ON, Canada.
Cynthia E HawkinsDepartment of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
Alberto BroniscerDivision of Pediatric Hematology-Oncology, Department of Pediatrics, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA. albertobroniscer5704@gmail.com.

Funding

VECTOR CORE FACILITYP30CA047904 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CHRISTOPHER J. BAKKENIST · 1988 to 2026
$158.0M
NCI NIH HHS P30 CA047904UPMC Hillman Cancer Center Core Laboratory P30CA047904
6 · The paper itself

Abstract

purposeTo characterize the clinical, radiological, and molecular characteristics of CNS tumors associated with Noonan syndrome (NS) and other non-Neurofibromatosis type 1 RASopathies.

methodsTwenty-four patients with concern for NS underwent clinical and central radiological review in this multi-institutional study. Whole-exome sequencing, RNA sequencing, and methylation analyses of peripheral blood and/or tumor specimens were performed.

resultsNineteen (79%) of 24 participants had NS, 17/19 (89%) of which had a germline PTPN11 variant; Nineteen of 24 participants (79%) were male. Seventeen of 19 (89%) patients with NS developed CNS tumors, including low-grade glioma, (LGG; pilocytic/pilomyxoid astrocytoma; n = 9) and dysembryoplastic neuroepithelial tumor (DNET; n = 6). Five patients incidentally diagnosed did not undergo histological confirmation. Radiological review showed multifocal parenchymal tumors in 9 patients with NS, including histologically confirmed neoplasm (n = 2), radiologic progression (n = 6), or typical tumoral imaging (n = 1). Fourteen of 15 (93%) tumors collected from 13 patients with NS and germline PTPN11 variants harbored somatic FGFR1 abnormalities. RNA sequencing of 12 tumors detected FGFR1 internal tandem duplication in one patient. Comparison with published data showed a statistically significant association between brain tumor occurrence and PTPN11-related NS, driven by two genotypes: NM_002834.5(PTPN11):c.182 A > G (p.Asp61Gly) and c.417G > T (p.Glu139Asp). Ten patients with CNS tumors, including 7/17 (41%) with PTPN11 variants, required chemotherapy. After median follow-up of 7.5 years, one patient died of CNS tumor.

conclusionPTPN11-related NS predisposes to multifocal low-grade glial and glioneuronal tumors confirmed by radiological, histological, and molecular characteristics. Targeting FGFR1-related pathways may provide new treatment approaches for patients with NS and low-grade CNS tumors.

Indexed as

Central Nervous System NeoplasmsMutationNoonan SyndromeProtein Tyrosine Phosphatase, Non-Receptor Type 11Receptor, Fibroblast Growth Factor, Type 1AdolescentAdultChildChild, PreschoolFemaleFollow-Up StudiesGenetic Predisposition to DiseaseGerm-Line MutationHumansInfantMaleFGFR1 protein, humanProtein Tyrosine Phosphatase, Non-Receptor Type 11PTPN11 protein, humanReceptor, Fibroblast Growth Factor, Type 1Brain tumorFGFR1GliomaNoonan syndromePTPN11

Identifiers

PMID41784910
PMCPMC12963110

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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.