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However, the recurrence rates varied widely in different case series, and to date, a unifying molecular genetic signature has not been identified. Among 1897 meningiomas resected at our institution, we identified 12 primary chordoid meningiomas from 12 patients. Histologically, all 12 cases had predominant (&gt;\u200950%) chordoid morphology. Ten were otherwise grade 1, and two were also atypical. We performed DNA global methylation profile, copy number variation analysis, and targeted next-generation sequencing on 11 chordoid meningiomas, and compared to those of 51 non-chordoid, mostly high grade meningiomas. The chordoid meningiomas demonstrated a unique methylation profile in tSNE, UMAP, and hierarchical heatmap clustering analyses of the most differentially methylated CpGs. The most common copy number variation in chordoid meningioma was loss of 1p (7\/11, 64%). Three chordoid meningiomas had 2p loss, which was significantly higher than the non-chordoid control cohort (27% vs 7.2%, <jats:italic>p<\/jats:italic>\u2009=\u20090.035). 22q loss was only seen in the two cases with additional atypical histological features. Chordoid meningiomas were enriched in mutations in chromatin remodeling genes <jats:italic>EP400<\/jats:italic> (8\/11,73%) <jats:italic>KMT2C<\/jats:italic> (4\/11, 36%) and <jats:italic>KMT2D<\/jats:italic> (4\/11, 36%), and showed low or absent <jats:italic>NF2, TERT, SMO<\/jats:italic>, and <jats:italic>AKT1<\/jats:italic> mutations. Prognosis wise, only one case recurred. This case had atypical histology and high-grade molecular features including truncating <jats:italic>NF2<\/jats:italic> mutation, 1p, 8p, 10, 14, 22q loss, and homozygous deletion of <jats:italic>CDKN2A\/B<\/jats:italic>. Progression free survival of chordoid, otherwise grade 1 meningioma was comparable to non-chordoid WHO grade 1 meningioma (<jats:italic>p<\/jats:italic>\u2009=\u20090.75), and significantly better than chordoid WHO grade 2 meningioma (<jats:italic>p<\/jats:italic>\u2009=\u20090.019). Conclusion: the chordoid histology alone may not justify a universal WHO grade 2 designation. Screening for additional atypical histological or molecular genetic features is recommended.<\/jats:p>","DOI":"10.1186\/s40478-022-01362-3","type":"journal-article","created":{"date-parts":[[2022,4,19]],"date-time":"2022-04-19T12:04:06Z","timestamp":1650369846000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Epigenetic and genomic profiling of chordoid meningioma: implications for clinical management"],"prefix":"10.1186","volume":"10","author":[{"given":"Elena V.","family":"Daoud","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kelsey","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruce","family":"Mickey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hussein","family":"Mohamed","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mandisa","family":"Wen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Delorenzo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivy","family":"Tran","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan","family":"Serrano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kimmo J.","family":"Hatanpaa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jack M.","family":"Raisanen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matija","family":"Snuderl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8808-4779","authenticated-orcid":false,"given":"Chunyu","family":"Cai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,4,19]]},"reference":[{"key":"1362_CR1","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-015-1940-9","author":"W Choy","year":"2015","unstructured":"Choy W, Ampie L, Lamano JB, Kesavabhotla K, Mao Q, Parsa AT, Bloch O (2015) Predictors of recurrence in the management of chordoid meningioma. 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