{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T12:27:57Z","timestamp":1793795277226,"version":"4.6.1"},"reference-count":26,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,5,14]],"date-time":"2022-05-14T00:00:00Z","timestamp":1652486400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,5,14]],"date-time":"2022-05-14T00:00:00Z","timestamp":1652486400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Yale School of Medicine, Department of Neurosurgery Clinical Sequencing Funds"},{"name":"Connecticut Brain Tumor Alliance"},{"name":"Gregory M. Kiez and Mehmet Kutman Foundation"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Med Genomics"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Multiple meningiomas (MMs) rarely occur sporadically. It is unclear whether each individual tumor in a single patient behaves similarly. Moreover, the molecular mechanisms underlying the formation of sporadic MMs and clonal formation etiology of these tumors are poorly understood.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Patients with spatially separated MMs without prior radiation exposure or a family history who underwent surgical resection of at least two meningiomas were included. Unbiased, comprehensive next generation sequencing was performed, and relevant clinical data was analyzed.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Fifteen\u00a0meningiomas and one\u00a0dural\u00a0specimen\u00a0from\u00a0six\u00a0patients\u00a0were\u00a0included.\u00a0The majority of tumors (12\/15) were WHO Grade I; one patient had bilateral MMs, one of which was Grade II, while the other was Grade I. We found 11\/15 of our cohort specimens were of <jats:italic>NF2<\/jats:italic>-loss subtype. Meningiomas from 5\/6 patients had a monoclonal origin, with the tumor from the remaining patient showing evidence for independent clonal formation. We identified a novel case of non-<jats:italic>NF2<\/jats:italic> mutant MM with monoclonal etiology. MMs due to a monoclonal origin did not always display a homogenous genomic profile, but rather exhibited heterogeneity due to branching evolution.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Both <jats:italic>NF2-<\/jats:italic>loss and non-<jats:italic>NF2<\/jats:italic> driven MMs can form due to monoclonal expansion and those tumors can acquire inter-tumoral heterogeneity through branched evolution. Grade I and II meningiomas can occur in the same patient. Thus, the molecular make-up and clinical behavior of one tumor in MMs, cannot reliably lend insight into that of the others and suggests the clinical management strategy for MMs should be tailored individually.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12920-022-01258-0","type":"journal-article","created":{"date-parts":[[2022,5,14]],"date-time":"2022-05-14T11:04:02Z","timestamp":1652526242000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Genomic profiling of sporadic multiple meningiomas"],"prefix":"10.1186","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1839-5912","authenticated-orcid":false,"given":"E. 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The study protocol was approved by the Human Investigations Committee and the Human Research Protection Program at Yale University. IRB approval from Yale University for this study\u2019s methods, along with written informed consent from all included study participants were obtained.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Written informed consent was obtained from all individual participants included in the study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no conflict of interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"112"}}