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Here, we analyzed 160 tumors from all 3 World Health Organization (WHO) grades (I through III) using clinical, gene expression, and sequencing data. Unsupervised clustering analysis identified 3 molecular types (A, B, and C) that reliably predicted recurrence. These groups did not directly correlate with the WHO grading system, which classifies more than half of the tumors in the most aggressive molecular type as benign. Transcriptional and biochemical analyses revealed that aggressive meningiomas involve loss of the repressor function of the DREAM complex, which results in cell-cycle activation; only tumors in this category tend to recur after full resection. These findings should improve our ability to predict recurrence and develop targeted treatments for these clinically challenging tumors.<\/jats:p>","DOI":"10.1073\/pnas.1912858116","type":"journal-article","created":{"date-parts":[[2019,10,7]],"date-time":"2019-10-07T20:36:32Z","timestamp":1570480592000},"page":"21715-21726","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":187,"title":["Molecular profiling predicts meningioma recurrence and reveals loss of DREAM complex repression in aggressive tumors"],"prefix":"10.1073","volume":"116","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1280-2989","authenticated-orcid":false,"given":"Akash J.","family":"Patel","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Baylor College of Medicine, Houston, TX 77030;"},{"name":"Jan and Dan Duncan Neurological Research Institute, Texas Children\u2019s Hospital, Houston, TX 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying-Wooi","family":"Wan","sequence":"additional","affiliation":[{"name":"Jan and Dan Duncan Neurological Research Institute, Texas Children\u2019s Hospital, Houston, TX 77030;"},{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rami","family":"Al-Ouran","sequence":"additional","affiliation":[{"name":"Jan and Dan Duncan Neurological Research Institute, Texas Children\u2019s Hospital, Houston, TX 77030;"},{"name":"Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Pierre","family":"Revelli","sequence":"additional","affiliation":[{"name":"Jan and Dan Duncan Neurological Research Institute, Texas Children\u2019s Hospital, Houston, TX 77030;"},{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria F.","family":"Cardenas","sequence":"additional","affiliation":[{"name":"Human Genome Sequencing Center, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mazen","family":"Oneissi","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Baylor College of Medicine, Houston, TX 77030;"},{"name":"Jan and Dan Duncan Neurological Research Institute, Texas Children\u2019s Hospital, Houston, TX 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liu","family":"Xi","sequence":"additional","affiliation":[{"name":"Human Genome Sequencing Center, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Jalali","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Baylor College of Medicine, Houston, TX 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2093-0603","authenticated-orcid":false,"given":"John F.","family":"Magnotti","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Baylor College of Medicine, Houston, TX 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna M.","family":"Muzny","sequence":"additional","affiliation":[{"name":"Human Genome Sequencing Center, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"HarshaVardhan","family":"Doddapaneni","sequence":"additional","affiliation":[{"name":"Human Genome Sequencing Center, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherly","family":"Sebastian","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Baylor College of Medicine, Houston, TX 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kent A.","family":"Heck","sequence":"additional","affiliation":[{"name":"Department of Pathology, Baylor College of Medicine, Houston, TX 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Clay","family":"Goodman","sequence":"additional","affiliation":[{"name":"Department of Pathology, Baylor College of Medicine, Houston, TX 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shankar P.","family":"Gopinath","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Baylor College of Medicine, Houston, TX 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7608-0831","authenticated-orcid":false,"given":"Zhandong","family":"Liu","sequence":"additional","affiliation":[{"name":"Jan and Dan Duncan Neurological Research Institute, Texas Children\u2019s Hospital, Houston, TX 77030;"},{"name":"Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ganesh","family":"Rao","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, TX 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9626-0936","authenticated-orcid":false,"given":"Sharon E.","family":"Plon","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030;"},{"name":"Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Yoshor","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Baylor College of Medicine, Houston, TX 77030;"},{"name":"Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Wheeler","sequence":"additional","affiliation":[{"name":"Human Genome Sequencing Center, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huda Y.","family":"Zoghbi","sequence":"additional","affiliation":[{"name":"Jan and Dan Duncan Neurological Research Institute, Texas Children\u2019s Hospital, Houston, TX 77030;"},{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030;"},{"name":"Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030;"},{"name":"Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030;"},{"name":"Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8182-384X","authenticated-orcid":false,"given":"Tiemo J.","family":"Klisch","sequence":"additional","affiliation":[{"name":"Jan and Dan Duncan Neurological Research Institute, Texas Children\u2019s Hospital, Houston, TX 77030;"},{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2019,10,7]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"iv1","DOI":"10.1093\/neuonc\/nov189","article-title":"CBTRUS statistical report: Primary brain and central nervous system tumors diagnosed in the United States in 2008-2012","volume":"17","author":"Ostrom Q. 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