{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T10:22:46Z","timestamp":1790418166536,"version":"4.1.0"},"reference-count":21,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T00:00:00Z","timestamp":1629763200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>Meningioma is the most common primary brain tumor, and recurrence risk increases with increasing WHO Grade from I to III. Rhabdoid meningiomas are a subset of WHO Grade III tumors with rhabdoid cells, a high proliferation index, and other malignant features that follow an aggressive clinical course. Some meningiomas with rhabdoid features either only focally or without other malignant features are classified as lower grade yet still recur early. Recently, inactivating mutations in the tumor suppressor gene <jats:italic>BAP1<\/jats:italic> have been associated with poorer prognosis in rhabdoid meningioma and meningioma with rhabdoid features, and germline mutations have been linked to a hereditary tumor predisposition syndrome (TPDS) predisposing patients primarily to melanoma and mesothelioma. We present the first report of a familial <jats:italic>BAP1<\/jats:italic> inactivating mutation identified after multiple generations of a family presented with meningiomas with rhabdoid features instead of with previously described <jats:italic>BAP1<\/jats:italic> loss-associated malignancies. A 24-year-old female presented with a Grade II meningioma with rhabdoid and papillary features treated with subtotal resection, adjuvant external beam radiation therapy, and salvage gamma knife radiosurgery six years later. Around that time, her mother presented with a meningioma with rhabdoid and papillary features managed with resection and adjuvant radiation therapy. Germline testing was positive for a pathogenic <jats:italic>BAP1<\/jats:italic> mutation in both patients. Sequencing of both tumors demonstrated biallelic <jats:italic>BAP1<\/jats:italic> inactivation <jats:italic>via<\/jats:italic> the combination of germline <jats:italic>BAP1<\/jats:italic> mutation and either loss of heterozygosity or somatic mutation. No additional mutations implicated in oncogenesis were noted from either patient\u2019s germline or tumor sequencing, suggesting that the inactivation of <jats:italic>BAP1<\/jats:italic> was responsible for pathogenesis. These cases demonstrate the importance of routine <jats:italic>BAP1<\/jats:italic> tumor testing in meningioma with rhabdoid features regardless of grade, germline testing for patients with <jats:italic>BAP1<\/jats:italic> inactivated tumors, and tailored cancer screening in this population.<\/jats:p>","DOI":"10.3389\/fonc.2021.721712","type":"journal-article","created":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T12:35:45Z","timestamp":1629808545000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":23,"title":["Germline BAP1 Mutation in a Family With Multi-Generational Meningioma With Rhabdoid Features: A Case Series and Literature Review"],"prefix":"10.3389","volume":"11","author":[{"given":"Rahul N.","family":"Prasad","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulysses G.","family":"Gardner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Yaney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel M.","family":"Prevedello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel C.","family":"Koboldt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana L.","family":"Thomas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine R.","family":"Mardis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua D.","family":"Palmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,8,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-016-1545-1","article-title":"The 2016 World Health Organization Classification of Tumors of the Central Nervous System: A Summary","volume":"131","author":"Louis","year":"2016","journal-title":"Acta Neuropathol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1093\/jnen\/nlv006","article-title":"Meningiomas With Rhabdoid Features Lacking Other Histologic Features of Malignancy: A Study of 44 Cases and Review of the Literature","volume":"75","author":"Vaubel","year":"2016","journal-title":"J Neuropathol Exp Neurol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1111\/j.1440-1789.2011.01201.x","article-title":"Rhabdoid Papillary Meningioma: A Clinicopathologic Case Series Study","volume":"31","author":"Wu","year":"2011","journal-title":"Neuropathology"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-19-1220","article-title":"Biological Mechanisms and Clinical Significance of BAP1 Mutations in Human Cancer","volume":"10","author":"Carbone","year":"2020","journal-title":"Cancer Discovery"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/now235","article-title":"Germline and Somatic BAP1 Mutations in High-Grade Rhabdoid Meningiomas","volume":"19","author":"Shankar","year":"2017","journal-title":"Neuro Oncol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/nox094","article-title":"BAP1 Mutations in High-Grade Meningioma: Implications for Patient Care","volume":"19","author":"Shankar","year":"2017","journal-title":"Neuro Oncol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2011-100156","article-title":"Germline BAP1 Mutation Predisposes to Uveal Melanoma, Lung Adenocarcinoma, Meningioma, and Other Cancers","volume":"48","author":"Abdel-Rahman","year":"2011","journal-title":"J Med Genet"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2015.09.011","article-title":"Germline BAP1 Mutation in a Family With High Incidence of Multiple Primary Cancers and a Potential Gene\u2013Environment Interaction","volume":"369","author":"Cheung","year":"2015","journal-title":"Cancer Letters"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12501","article-title":"A Recurrent Germline BAP1 Mutation and Extension of the BAP1 Tumor Predisposition Spectrum to Include Basal Cell Carcinoma","volume":"88","author":"Wadt K a","year":"2015","journal-title":"Clin Genet"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3892\/or_00000032","article-title":"Sstr2A Immunohistochemical Expression in Human Meningiomas: Is There a Correlation With the Histological Grade, Proliferation or Microvessel Density","volume":"20","author":"Barresi","year":"2008","journal-title":"Oncol Rep"},{"key":"B11","article-title":"Expression of Somatostatin Receptors (SSTR1-SSTR5) in Meningiomas and its Clinicopathological Significance","volume":"8","author":"Silva CB de","year":"2015","journal-title":"Int J Clin Exp Pathol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-020-01568-6","article-title":"The Spatial Phenotype of Genotypically Distinct Meningiomas Demonstrate Potential Implications of the Embryology of the Meninges","volume":"40","author":"Fountain","year":"2021","journal-title":"Oncogene"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-18-4093","article-title":"Inactivation of Bap1 Cooperates With Losses of Nf2 and Cdkn2a to Drive the Development of Pleural Malignant Mesothelioma in Conditional Mouse Models","volume":"79","author":"Kukuyan","year":"2019","journal-title":"Cancer Res"},{"key":"B14","doi-asserted-by":"publisher","first-page":"999","DOI":"10.1001\/jamadermatol.2017.2330","article-title":"Genotypic and Phenotypic Features of BAP1 Cancer Syndrome: A Report of 8 New Families and Review of Cases in the Literature","volume":"153","author":"Haugh","year":"2017","journal-title":"JAMA Dermatol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.cancergen.2015.12.007","article-title":"A Novel BAP1 Mutation is Associated With Melanocytic Neoplasms and Thyroid Cancer","volume":"209","author":"McDonnell","year":"2016","journal-title":"Cancer Genet"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/nov316","article-title":"Oncogenic PI3K Mutations are as Common as AKT1 and SMO Mutations in Meningioma","volume":"18","author":"Abedalthagafi","year":"2016","journal-title":"Neuro Oncol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-005-0021-0","article-title":"Rare Mutation of PIK3CA in Meningiomas","volume":"111","author":"Pang","year":"2006","journal-title":"Acta Neuropathol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/now029","article-title":"PIK3CA Mutations in Meningioma","volume":"18","author":"Zadeh","year":"2016","journal-title":"Neuro Oncol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.19.02263","article-title":"Growth Rates of Genetically Defined Renal Tumors: Implications for Active Surveillance and Intervention","volume":"38","author":"Ball","year":"2020","journal-title":"JCO"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.wneu.2018.06.227","article-title":"Giant Pediatric Rhabdoid Meningioma Associated With a Germline BAP1 Pathogenic Variation: A Rare Clinical Case","volume":"119","author":"Ravanpay","year":"2018","journal-title":"World Neurosurgery"},{"key":"B21","doi-asserted-by":"publisher","first-page":"1114","DOI":"10.3390\/cancers11081114","article-title":"Families With BAP1-Tumor Predisposition Syndrome in the Netherlands: Path to Identification and a Proposal for Genetic Screening Guidelines","volume":"11","author":"Chau","year":"2019","journal-title":"Cancers (Basel)"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2021.721712\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T12:35:48Z","timestamp":1629808548000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2021.721712\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,24]]},"references-count":21,"alternative-id":["10.3389\/fonc.2021.721712"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2021.721712","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,24]]},"article-number":"721712"}}