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

Autor: 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., 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., 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., 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., 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., 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., 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., 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., 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., 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., 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., 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., 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., 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., Avşar T; Department of Neurosurgery, Bahcesehir University, School of Medicine, Istanbul, Turkey., Bayri Y; Department of Neurosurgery, Marmara University School of Medicine, 34854, Istanbul, Turkey., Schramm J; University of Bonn Medical School, 53105, Bonn, Germany., 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., Peyre M; Department of Neurosurgery, Hopital Pitie-Salpetriere, AP-HP & Sorbonne Université, F-75103, Paris, France., Riche M; Department of Neurosurgery, Hopital Pitie-Salpetriere, AP-HP & Sorbonne Université, F-75103, Paris, France., Goldbrunner R; Center for Neurosurgery, University Hospital of Cologne, 50937, Cologne, Germany., Amankulor N; Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA, USA., 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., 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., Pamir MN; Department of Neurosurgery, Acibadem Mehmet Ali Aydınlar University, School of Medicine, Istanbul, 34848, Turkey., Özduman K; Department of Neurosurgery, Acibadem Mehmet Ali Aydınlar University, School of Medicine, Istanbul, 34848, Turkey., Kilic T; Department of Neurosurgery, Bahcesehir University, School of Medicine, Istanbul, Turkey., Knight JR; Yale Center for Genome Analysis, Yale University West Campus, Orange, CT, USA., Simon M; University of Bonn Medical School, 53105, Bonn, Germany.; Department of Neurosurgery, Bethel Clinic, University of Bielefeld Medical Center OWL, Bielefeld, Germany., 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., Kalamarides M; Department of Neurosurgery, Hopital Pitie-Salpetriere, AP-HP & Sorbonne Université, F-75103, Paris, France., Timmer M; Center for Neurosurgery, University Hospital of Cologne, 50937, Cologne, Germany., 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., 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., 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., 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., 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.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Oct 07; Vol. 14 (1), pp. 6279. Date of Electronic Publication: 2023 Oct 07.
DOI: 10.1038/s41467-023-41926-y
Abstrakt: 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.
(© 2023. Springer Nature Limited.)
Databáze: MEDLINE
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