Evidence map›Paper›PMID 39495206›Full record

ArticleCancer research2025

FOXR2 Targets LHX6+/DLX+ Neural Lineages to Drive Central Nervous System Neuroblastoma.

Selin Jessa, Antonella De Cola, Bhavyaa Chandarana, Michael McNicholas, Steven Hébert, Adam Ptack, Damien Faury, Jessica W Tsai, Andrey Korshunov, Timothy N Phoenix and 7 more

Abstract read
In one paragraph

Article in Cancer research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Histopathology and Molecular Pathology of Pineal Region Tumors.Advances and technical standards in neurosurgery · 2026
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors.

Selin Jessa *Lady Davis Research Institute, Jewish General Hospital, Montreal, Canada.ORCID 0000-0003-4192-6523
Antonella De Cola *Department of Oncology, Early Cancer Institute, Adrian Way, University of Cambridge, Cambridge, United Kingdom.ORCID 0000-0002-3202-5339
Bhavyaa Chandarana *Lady Davis Research Institute, Jewish General Hospital, Montreal, Canada.ORCID 0009-0002-7972-2892
Michael McNicholasDepartment of Oncology, Early Cancer Institute, Adrian Way, University of Cambridge, Cambridge, United Kingdom.ORCID 0000-0002-6920-9924
Steven HébertLady Davis Research Institute, Jewish General Hospital, Montreal, Canada.ORCID 0000-0001-6267-8595
Adam PtackDepartment of Experimental Medicine, McGill University, Montreal, Canada.ORCID 0009-0000-5020-1722
Damien FauryResearch Institute of the McGill University Health Centre, Montreal, Canada.ORCID 0000-0003-1584-599X
Jessica W TsaiDepartment of Pediatrics, Keck School of Medicine of University of Southern California, Los Angeles, California.ORCID 0000-0003-0540-4330
Andrey KorshunovClinical Cooperation Unit Neuropathology (B300), German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), National Center for Tumor Diseases (NCT), Heidelberg, Germany.ORCID 0000-0001-9408-6578
Timothy N PhoenixDivision of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, Ohio.ORCID 0000-0003-4771-4003
Benjamin EllezamDepartment of Pathology, Centre Hospitalier Universitaire Sainte-Justine, Université de Montréal, Montréal, Canada.ORCID 0000-0002-8716-7924
David T W JonesDivision of Pediatric Glioma Research, Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany.ORCID 0000-0002-2036-5141
Michael D TaylorPediatric Neuro-Oncology Research Program, Texas Children's Hospital, Houston, Texas.ORCID 0000-0001-7009-3466
Pratiti BandopadhayayBroad Institute of MIT and Harvard, Cambridge, Massachusetts.ORCID 0000-0002-4175-4760
Manav PathaniaDepartment of Oncology, Early Cancer Institute, Adrian Way, University of Cambridge, Cambridge, United Kingdom.ORCID 0000-0001-5635-5028
Nada JabadoDepartment of Human Genetics, McGill University, Montreal, Canada.ORCID 0000-0003-2485-3692
Claudia L KleinmanLady Davis Research Institute, Jewish General Hospital, Montreal, Canada.ORCID 0000-0002-5158-7126

Funding

Deciphering the Role of Aberrant Endogenous Retroviral Expression in Onco-histone Driven GliomaR01NS116361 · NINDS · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI Stephen C Mack · 2021 to 2026
$2.5M
Alex's Lemonade Stand Foundation for Childhood Cancer (ALSF)Brain Research UK (BRUK) 202021-28Calcul QuebecCanadian Institutes of Health Research (CIHR)Canadian Institutes of Health Research (CIHR) PJT-156086Canadian Institutes of Health Research (CIHR) PJT-190271Cancer Research UK Cambridge Institute, University of Cambridge (CRUK CI)Cancer Research UK (CRUK) Award RCCCEA-May22\100003Emily Parsons DonationFaculty of Medicine, McGill University (McGill Faculty of Medicine)Fondation Charles-Bruneau (Charles Bruneau Foundation)Fonds de Recherche du Québec - Santé (FRQS)Genome Canada (GC)Great Ormond Street Hospital Charity (GOSH) V4020Griffin's GuardiansHelen Gurley Brown Presidential InitiativeKids Join the FightLady Davis Institute for Medical Research (LDI)National Institute of Neurological Disorders and Stroke (NINDS) R01NS116361Natural Sciences and Engineering Research Council of Canada (NSERC) RGPIN-2016-04911NINDS NIH HHS R01 NS116361Pedals for PediatricsRally Foundation (Rally Foundation, Inc.)St. Baldrick's Foundation (SBF)
6 · The paper itself

Abstract

Central nervous system neuroblastoma with forkhead box R2 (FOXR2) activation (NB-FOXR2) is a high-grade tumor of the brain hemispheres and a newly identified molecular entity. Tumors express dual neuronal and glial markers, leading to frequent misdiagnoses, and limited information exists on the role of FOXR2 in their genesis. To identify their cellular origins, we profiled the transcriptomes of NB-FOXR2 tumors at the bulk and single-cell levels and integrated these profiles with large single-cell references of the normal brain. NB-FOXR2 tumors mapped to LHX6+/DLX+ lineages derived from the medial ganglionic eminence, a progenitor domain in the ventral telencephalon. In vivo prenatal Foxr2 targeting to the ganglionic eminences in mice induced postnatal cortical tumors recapitulating human NB-FOXR2-specific molecular signatures. Profiling of FOXR2 binding on chromatin in murine models revealed an association with ETS transcriptional networks, as well as direct binding of FOXR2 at key transcription factors that coordinate initiation of gliogenesis. These data indicate that NB-FOXR2 tumors originate from LHX6+/DLX+ interneuron lineages, a lineage of origin distinct from that of other FOXR2-driven brain tumors, highlight the susceptibility of ventral telencephalon-derived interneurons to FOXR2-driven oncogenesis, and suggest that FOXR2-induced activation of glial programs may explain the mixed neuronal and oligodendroglial features in these tumors. More broadly, this work underscores systematic profiling of brain development as an efficient approach to orient oncogenic targeting for in vivo modeling, critical for the study of rare tumors and development of therapeutics. Significance: Profiling the developing brain enabled rationally guided modeling of FOXR2-activated CNS neuroblastoma, providing a strategy to overcome the heterogeneous origins of pediatric brain tumors that hamper tumor modeling and therapy development. See related commentary by Orr, p. 195.

Indexed as

Brain NeoplasmsCentral Nervous System NeoplasmsForkhead Transcription FactorsHomeodomain ProteinsLIM-Homeodomain ProteinsNerve Tissue ProteinsNeuroblastomaTranscription FactorsAnimalsCell LineageGene Expression Regulation, NeoplasticHumansMiceNeuronsForkhead Transcription FactorsFOXR2 protein, humanHomeodomain ProteinsLHX6 protein, humanLIM-Homeodomain ProteinsNerve Tissue ProteinsTranscription Factors

Identifiers

PMID39495206
PMCPMC11733536

What OpenQuestion 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 OpenQuestion graph.