{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T02:40:24Z","timestamp":1791945624264,"version":"4.3.4"},"reference-count":81,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2024,8,2]],"date-time":"2024-08-02T00:00:00Z","timestamp":1722556800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005946","name":"The Jackson Laboratory","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005946","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30CA034196"],"award-info":[{"award-number":["P30CA034196"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 CA262311"],"award-info":[{"award-number":["R01 CA262311"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01NS118039"],"award-info":[{"award-number":["R01NS118039"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01NS117104"],"award-info":[{"award-number":["R01NS117104"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P50CA221747"],"award-info":[{"award-number":["P50CA221747"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Lou and Jean Malnati Brain Tumor Institute"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Advances in our understanding of the molecular biology of meningiomas have led to significant gains in the ability to predict patient prognosis and tumor recurrence and to identify novel targets for therapeutic design. Specifically, classification of meningiomas based on DNA methylation has greatly improved our ability to risk stratify patients, however new questions have arisen in terms of the underlying impact these DNA-methylation signatures have on meningioma biology.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>This study utilizes RNA-sequencing data from 486 meningioma samples corresponding to 3 meningioma DNA-methylation groups (merlin-intact, immune-enriched, and hypermitotic), followed by in vitro experiments utilizing human meningioma cell lines.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We identify alterations in RNA splicing between meningioma DNA-methylation groups including individual splicing events that correlate with hypermitotic meningiomas and predict tumor recurrence and overall patient prognosis and compile a set of splicing events that can accurately predict DNA-methylation classification based on RNA-seq data. Furthermore, we validate these events using reverse transcription polymerase chain reaction (RT-PCR) in patient samples and meningioma cell lines. Additionally, we identify alterations in RNA-binding proteins and splicing factors that lie upstream of RNA splicing events, including upregulation of SRSF1 in hypermitotic meningiomas which we show drives alternative RNA splicing changes. Finally, we design splice-switching antisense oligonucleotides to target RNA splicing changes in NASP and MFF observed in hypermitotic meningiomas, providing a rationale for RNA-based therapeutic design.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>RNA splicing is an important driver of meningioma phenotypes that can be useful in prognosticating patients and as a potential exploit for therapeutic vulnerabilities.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/neuonc\/noae150","type":"journal-article","created":{"date-parts":[[2024,8,2]],"date-time":"2024-08-02T16:21:09Z","timestamp":1722615669000},"page":"2222-2236","source":"Crossref","is-referenced-by-count":9,"title":["RNA splicing as a biomarker and phenotypic driver of meningioma DNA-methylation groups"],"prefix":"10.1093","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0401-2549","authenticated-orcid":false,"given":"Nathan K","family":"Leclair","sequence":"first","affiliation":[{"name":"Graduate Program in Genetics and Development, UConn Health , Farmington, CT ,","place":["USA"]},{"name":"The Jackson Laboratory for Genomic Medicine , Farmington, CT ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abrar","family":"Choudury","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of California San Francisco , San Francisco, CA ,","place":["USA"]},{"name":"Department of Neurological Surgery, University of California San Francisco , San Francisco, CA,","place":["USA"]},{"name":"Department of Radiation Oncology, University of California San Francisco , San Francisco, CA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William C","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of California San Francisco , San Francisco, CA ,","place":["USA"]},{"name":"Department of Neurological Surgery, University of California San Francisco , San Francisco, CA,","place":["USA"]},{"name":"Department of Radiation Oncology, University of California San Francisco , San Francisco, CA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen T","family":"Magill","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Northwestern University , Chicago, IL ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"McCortney","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Northwestern University , Chicago, IL ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig M","family":"Horbinski","sequence":"additional","affiliation":[{"name":"Department of Pathology, Northwestern University , Chicago, IL ,","place":["USA"]},{"name":"Department of Neurological Surgery, Northwestern University , Chicago, IL ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenhong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of California San Francisco , San Francisco, CA ,","place":["USA"]},{"name":"Department of Neurological Surgery, University of California San Francisco , San Francisco, CA,","place":["USA"]},{"name":"Department of Radiation Oncology, University of California San Francisco , San Francisco, CA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ezequiel","family":"Goldschmidt","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, University of California San Francisco , San Francisco, CA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte D","family":"Eaton","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of California San Francisco , San Francisco, CA ,","place":["USA"]},{"name":"Department of Neurological Surgery, University of California San Francisco , San Francisco, CA,","place":["USA"]},{"name":"Department of Radiation Oncology, University of California San Francisco , San Francisco, CA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ketan R","family":"Bulsara","sequence":"additional","affiliation":[{"name":"Division of Neurosurgery, Department of Surgery, UConn Health , Farmington, CT ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenya Linda","family":"Bi","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute , Boston, MA ,","place":["USA"]},{"name":"Department of Neurosurgery, Brigham and Women\u2019s Hospital , Boston, MA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akash J","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Baylor College of Medicine , Houston, TX ,","place":["USA"]},{"name":"Jan and Dan Duncan Neurological Research Institute, Texas Children\u2019s Hospital , Houston, TX ,","place":["USA"]},{"name":"Department of Neurosurgery, Baylor College of Medicine , Houston, TX ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5441-1962","authenticated-orcid":false,"given":"Felix","family":"Sahm","sequence":"additional","affiliation":[{"name":"CCU Neuropathology, German Consortium for Translational Cancer Research, German Cancer Research Center , Heidelberg,","place":["Germany"]},{"name":"Department of Neuropathology, University Hospital Heidelberg , Heidelberg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9299-8864","authenticated-orcid":false,"given":"David","family":"Raleigh","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of California San Francisco , San Francisco, CA ,","place":["USA"]},{"name":"Department of Neurological Surgery, University of California San Francisco , San Francisco, CA,","place":["USA"]},{"name":"Department of Radiation Oncology, University of California San Francisco , San Francisco, CA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0516-2677","authenticated-orcid":false,"given":"Olga","family":"Anczukow","sequence":"additional","affiliation":[{"name":"Institute for Systems Genomics, UConn Health , Farmington, CT,","place":["USA"]},{"name":"Department of Genetics and Genome Sciences, UConn Health , Farmington, 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