{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T16:11:03Z","timestamp":1784045463994,"version":"3.55.0"},"reference-count":18,"publisher":"S. Karger AG","issue":"4","license":[{"start":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T00:00:00Z","timestamp":1769472000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"},{"start":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T00:00:00Z","timestamp":1769472000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathobiology"],"abstract":"<jats:p>Introduction: The subependymal giant cell astrocytoma (SEGA) predominantly occurs in patients with tuberous sclerosis. Here, we present an unusual aggressive transformation of SEGA-imitating fibrous meningioma in a child carrying a germline CHEK2 mutation. Methods: This case study was conducted at a tertiary pediatric oncology center in accordance with current diagnostic and therapeutic standards. Tumor classification followed WHO CNS5 criteria and was complemented by genome-wide DNA methylation profiling. Comprehensive molecular workup included germline and somatic whole exome sequencing, copy number analysis, and RNA sequencing. Results: An 8.5-year-old girl presented with an intraventricular tumor initially diagnosed as SEGA based on imaging and partial resection histology. Treatment with an mTOR inhibitor led to 4 years of stability before rapid progression and death due to postoperative brain edema. Re-examination of both specimens revealed transformation into an aggressive anaplastic meningioma, while the initial lesion was reclassified as fibrous meningioma. Whole exome and microarray analyses excluded germline TSC1\/TSC2 defects but identified a pathogenic germline CHEK2 variant (c.1466del, p.Asn489ThrfsTer23). Somatic alterations involving NF1 and TP53 were found in the primary tumor. Conclusions: Constitutional CHEK2 mutations combined with somatic NF1 defect may have promoted the malignant progression of SEGA-imitating fibrous meningioma and its favorable initial response to mTOR inhibitors.<\/jats:p>","DOI":"10.1159\/000550591","type":"journal-article","created":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T17:02:15Z","timestamp":1769533335000},"page":"246-254","source":"Crossref","is-referenced-by-count":0,"title":["Malignant Progression of Subependymal Giant Cell Astrocytoma-Imitating Fibrous Meningioma in a Child Carrying a Germline CHEK2 Mutation"],"prefix":"10.1159","volume":"93","author":[{"given":"Bartosz","family":"Szmyd","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3804-7042","authenticated-orcid":false,"given":"Marcin","family":"Braun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agata","family":"Pastorczak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9971-9677","authenticated-orcid":false,"given":"Dariusz 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