{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T13:40:29Z","timestamp":1791380429691,"version":"4.3.3"},"reference-count":53,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"43","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2024,10,25]]},"abstract":"<jats:p>\n            An important subset of meningiomas behaves aggressively and is characterized by multiple recurrences. We identify clinical, genetic, and epigenetic predictors of multiply recurrent meningiomas (MRMs) and evaluate the evolution of these meningiomas in patient-matched samples. On multivariable binomial logistic regression, MRMs were significantly associated with male sex (\n            <jats:italic>P<\/jats:italic>\n            = 0.012), subtotal resection (\n            <jats:italic>P<\/jats:italic>\n            = 0.001), higher number of meningiomas on presentation (\n            <jats:italic>P<\/jats:italic>\n            = 0.017), and histopathological sheeting (\n            <jats:italic>P<\/jats:italic>\n            = 0.002). Multiomic analysis of primary meningiomas revealed that MRMs have greater copy number losses (\n            <jats:italic>P<\/jats:italic>\n            = 0.0313) and increased DNA methylation (\n            <jats:italic>P<\/jats:italic>\n            = 0.0155). In meningioma cells with knockdown of\n            <jats:italic>\n              <jats:italic>EDNRB<\/jats:italic>\n            <\/jats:italic>\n            , a locus with greater promoter methylation and decreased gene expression in MRMs had increased proliferation (\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.0001). MRM recurrences were found to be similar to primaries but have a greater burden of copy number gains (\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.0001) and increased methylation (\n            <jats:italic>P<\/jats:italic>\n            = 0.0045). This clinical and multiomic investigation of MRMs harbors implications for the future development of biomarkers and therapeutic agents for these challenging tumors.\n          <\/jats:p>","DOI":"10.1126\/sciadv.adn4419","type":"journal-article","created":{"date-parts":[[2024,10,23]],"date-time":"2024-10-23T17:58:43Z","timestamp":1729706323000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":11,"title":["Multiomic and clinical analysis of multiply recurrent meningiomas reveals risk factors, underlying biology, and insights into evolution"],"prefix":"10.1126","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5179-5232","authenticated-orcid":true,"given":"Sangami","family":"Pugazenthi","sequence":"first","affiliation":[{"name":"Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8062-7310","authenticated-orcid":true,"given":"Bhuvic","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO, USA."},{"name":"The Brain Tumor Center, Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3730-2793","authenticated-orcid":true,"given":"Collin W.","family":"English","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Baylor College of Medicine, Houston, TX, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William A.","family":"Leidig","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO, 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USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6483-9153","authenticated-orcid":true,"given":"Kaleigh","family":"Roberts","sequence":"additional","affiliation":[{"name":"Department of Neuropathology, Washington University School of Medicine, St. Louis, MO, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1309-9612","authenticated-orcid":true,"given":"Ajay","family":"Chatrath","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Baylor College of Medicine, Houston, TX, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ron","family":"Gadot","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, 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Houston, TX, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6374-9041","authenticated-orcid":true,"given":"Akdes S.","family":"Harmanci","sequence":"additional","affiliation":[{"name":"The Brain Tumor Center, Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA."},{"name":"Center for Cancer Neuroscience, Baylor College of Medicine, Houston, TX, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1280-2989","authenticated-orcid":true,"given":"Akash J.","family":"Patel","sequence":"additional","affiliation":[{"name":"The Brain Tumor Center, Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA."},{"name":"Jan and Dan Duncan Neurological Research Institute, Texas Children\u2019s Hospital, Houston, TX, USA."},{"name":"Center for Cancer Neuroscience, Baylor College of Medicine, Houston, TX, USA."},{"name":"Department of 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