Super-enhancer hijacking drives ectopic expression of hedgehog pathway ligands in meningiomas.

Humans Hedgehog Proteins / genetics Meningioma / genetics Ligands Signal Transduction Meningeal Neoplasms / genetics

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
07 10 2023
Historique:
received: 11 08 2022
accepted: 25 09 2023
medline: 1 11 2023
pubmed: 8 10 2023
entrez: 7 10 2023
Statut: epublish

Résumé

Hedgehog signaling mediates embryologic development of the central nervous system and other tissues and is frequently hijacked by neoplasia to facilitate uncontrolled cellular proliferation. Meningiomas, the most common primary brain tumor, exhibit Hedgehog signaling activation in 6.5% of cases, triggered by recurrent mutations in pathway mediators such as SMO. In this study, we find 35.6% of meningiomas that lack previously known drivers acquired various types of somatic structural variations affecting chromosomes 2q35 and 7q36.3. These cases exhibit ectopic expression of Hedgehog ligands, IHH and SHH, respectively, resulting in Hedgehog signaling activation. Recurrent tandem duplications involving IHH permit de novo chromatin interactions between super-enhancers within DIRC3 and a locus containing IHH. Our work expands the landscape of meningioma molecular drivers and demonstrates enhancer hijacking of Hedgehog ligands as a route to activate this pathway  in neoplasia.

Identifiants

DOI: 10.1038/s41467-023-41926-y PMID: 37805627 PMC: PMC10560290
pubmed: 37805627
doi: 10.1038/s41467-023-41926-y
pii: 10.1038/s41467-023-41926-y
pmc: PMC10560290
doi:

Substances chimiques

Hedgehog Proteins 0
Ligands 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

6279

Subventions

Organisme : NCI NIH HHS
ID : P50 CA221747
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA060553
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS120547
Pays : United States
Organisme : NCI NIH HHS
ID : F30 CA183530
Pays : United States
Organisme : NCI NIH HHS
ID : F30 CA213666
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007205
Pays : United States

Informations de copyright

© 2023. Springer Nature Limited.

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Auteurs

Mark W Youngblood (MW)

Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, CT, USA.
Department of Neurosurgery, Yale School of Medicine, New Haven, CT, USA.
Department of Genetics, Yale School of Medicine, New Haven, CT, USA.
Department of Neurological Surgery, Malnati Brain Tumor Institute of the Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
ORCID: 0000-0002-1044-8015

Zeynep Erson-Omay (Z)

Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, CT, USA.
Department of Neurosurgery, Yale School of Medicine, New Haven, CT, USA.

Chang Li (C)

Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, CT, USA.
Department of Neurosurgery, Yale School of Medicine, New Haven, CT, USA.
Department of Neurosurgery, Sun Yat-sen University Cancer Center, 510060, Guangzhou, P. R. China.

Hinda Najem (H)

Department of Neurological Surgery, Malnati Brain Tumor Institute of the Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
ORCID: 0000-0003-4432-9708

Süleyman Coșkun (S)

Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, CT, USA.
Department of Neurosurgery, Yale School of Medicine, New Haven, CT, USA.
Department of Biological Sciences, Middle East Technical University, 06800, Ankara, Turkey.

Evgeniya Tyrtova (E)

Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, CT, USA.
Department of Neurosurgery, Yale School of Medicine, New Haven, CT, USA.
Department of Neurosurgery, University of Washington, Seattle, WA, USA.

Julio D Montejo (JD)

Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, CT, USA.
Department of Neurosurgery, Yale School of Medicine, New Haven, CT, USA.
Section of Neurosurgery, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA.
ORCID: 0000-0003-2166-4861

Danielle F Miyagishima (DF)

Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, CT, USA.
Department of Neurosurgery, Yale School of Medicine, New Haven, CT, USA.
Department of Genetics, Yale School of Medicine, New Haven, CT, USA.
ORCID: 0000-0003-3257-5469

Tanyeri Barak (T)

Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, CT, USA.
Department of Neurosurgery, Yale School of Medicine, New Haven, CT, USA.

Sayoko Nishimura (S)

Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, CT, USA.
Department of Neurosurgery, Yale School of Medicine, New Haven, CT, USA.
ORCID: 0009-0008-8396-1267

Akdes Serin Harmancı (AS)

Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, CT, USA.
Department of Neurosurgery, Yale School of Medicine, New Haven, CT, USA.
Department of Neurosurgery, Baylor College of Medicine, Houston, TX, 77030, USA.

Victoria E Clark (VE)

Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, CT, USA.
Department of Neurosurgery, Yale School of Medicine, New Haven, CT, USA.
Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.

Daniel Duran (D)

Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, CT, USA.
Department of Neurosurgery, Yale School of Medicine, New Haven, CT, USA.
Department of Neurosurgery, University of Mississippi Medical Center, Jackson, MS, 39216, USA.
ORCID: 0000-0001-6888-252X

Anita Huttner (A)

Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, CT, USA.
Department of Pathology, Yale School of Medicine, New Haven, CT, USA.

Timuçin Avşar (T)

Department of Neurosurgery, Bahcesehir University, School of Medicine, Istanbul, Turkey.

Yasar Bayri (Y)

Department of Neurosurgery, Marmara University School of Medicine, 34854, Istanbul, Turkey.

Johannes Schramm (J)

University of Bonn Medical School, 53105, Bonn, Germany.

Julien Boetto (J)

Department of Neurosurgery, Hopital Pitie-Salpetriere, AP-HP & Sorbonne Université, F-75103, Paris, France.
Department of Neurosurgery, Gui de Chauliac Hospital, Montpellier University Medical Center, Montpellier, France.

Matthieu Peyre (M)

Department of Neurosurgery, Hopital Pitie-Salpetriere, AP-HP & Sorbonne Université, F-75103, Paris, France.
ORCID: 0000-0001-8470-9516

Maximilien Riche (M)

Department of Neurosurgery, Hopital Pitie-Salpetriere, AP-HP & Sorbonne Université, F-75103, Paris, France.

Roland Goldbrunner (R)

Center for Neurosurgery, University Hospital of Cologne, 50937, Cologne, Germany.

Nduka Amankulor (N)

Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA, USA.

Angeliki Louvi (A)

Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, CT, USA.
Department of Neurosurgery, Yale School of Medicine, New Haven, CT, USA.
ORCID: 0000-0003-1737-8707

Kaya Bilgüvar (K)

Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, CT, USA.
Department of Neurosurgery, Yale School of Medicine, New Haven, CT, USA.
Department of Genetics, Yale School of Medicine, New Haven, CT, USA.
Yale Center for Genome Analysis, Yale University West Campus, Orange, CT, USA.
Department of Medical Genetics Acibadem Mehmet Ali Aydınlar University, School of Medicine, Istanbul, 34848, Turkey.

M Necmettin Pamir (MN)

Department of Neurosurgery, Acibadem Mehmet Ali Aydınlar University, School of Medicine, Istanbul, 34848, Turkey.

Koray Özduman (K)

Department of Neurosurgery, Acibadem Mehmet Ali Aydınlar University, School of Medicine, Istanbul, 34848, Turkey.

Türker Kilic (T)

Department of Neurosurgery, Bahcesehir University, School of Medicine, Istanbul, Turkey.

James R Knight (JR)

Yale Center for Genome Analysis, Yale University West Campus, Orange, CT, USA.
ORCID: 0000-0003-1166-0437

Matthias Simon (M)

University of Bonn Medical School, 53105, Bonn, Germany.
Department of Neurosurgery, Bethel Clinic, University of Bielefeld Medical Center OWL, Bielefeld, Germany.

Craig Horbinski (C)

Department of Neurological Surgery, Malnati Brain Tumor Institute of the Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
ORCID: 0000-0001-8340-9992

Michel Kalamarides (M)

Department of Neurosurgery, Hopital Pitie-Salpetriere, AP-HP & Sorbonne Université, F-75103, Paris, France.

Marco Timmer (M)

Center for Neurosurgery, University Hospital of Cologne, 50937, Cologne, Germany.

Amy B Heimberger (AB)

Department of Neurological Surgery, Malnati Brain Tumor Institute of the Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
ORCID: 0000-0002-9970-8695

Ketu Mishra-Gorur (K)

Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, CT, USA.
Department of Neurosurgery, Yale School of Medicine, New Haven, CT, USA.
ORCID: 0000-0002-3182-4411

Jennifer Moliterno (J)

Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, CT, USA.
Department of Neurosurgery, Yale School of Medicine, New Haven, CT, USA.
Yale Cancer Center, Yale School of Medicine, New Haven, CT, USA.

Katsuhito Yasuno (K)

Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, CT, USA. katsuhito.yasuno@yale.edu.
Department of Neurosurgery, Yale School of Medicine, New Haven, CT, USA. katsuhito.yasuno@yale.edu.
ORCID: 0000-0002-3606-532X

Murat Günel (M)

Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, CT, USA. murat.gunel@yale.edu.
Department of Neurosurgery, Yale School of Medicine, New Haven, CT, USA. murat.gunel@yale.edu.
Department of Genetics, Yale School of Medicine, New Haven, CT, USA. murat.gunel@yale.edu.
Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA, USA. murat.gunel@yale.edu.
Yale Cancer Center, Yale School of Medicine, New Haven, CT, USA. murat.gunel@yale.edu.
ORCID: 0000-0002-2290-7055

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Super-enhancer hijacking drives ectopic...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Protéines Hedgehog › Super-enhancer hijacking drives ectopic...
questionsmedicales.fr › Maladies du système nerveux › Tumeurs du système nerveux › Tumeurs du système nerveux central › Tumeurs des méninges › Méningiome › Super-enhancer hijacking drives ectopic...
questionsmedicales.fr › Actions chimiques et utilisations › Utilisations spécialisées de produits chimiques › Produits chimiques de laboratoire › Ligands › Super-enhancer hijacking drives ectopic...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Super-enhancer hijacking drives ectopic...
questionsmedicales.fr › Maladies du système nerveux › Tumeurs du système nerveux › Tumeurs du système nerveux central › Tumeurs des méninges › Super-enhancer hijacking drives ectopic...