{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T20:31:59Z","timestamp":1774470719546,"version":"3.50.1"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,12,16]],"date-time":"2021-12-16T00:00:00Z","timestamp":1639612800000},"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>As an oncogenic somatic variant, telomerase reverse transcriptase promoter (TERTp) mutations are frequently observed in adult glioblastoma (GBM). Alternatively, we report the first case of glioblastoma with TERT amplification accompanied by multiple TERT and FGFR2 gene fusions instead of TERTp mutation. A 55-year-old woman presented with dizziness, headache, and diplopia for three weeks. Magnetic resonance imaging (MRI) demonstrated a heterogeneously enhancing lobulated mass centered in the pineal region. Partial tumor resection and ventriculoperitoneal shunt were achieved, and the residual tumor was then treated with standard radiation. The tumor was diagnosed as GBM, IDH-wild type, WHO grade IV, and the Ki67 proliferation index was high (30\u201340%). Intriguingly, TERT amplification without TERTp mutation was identified <jats:italic>via<\/jats:italic> next generation sequencing (NGS). Further analysis revealed multiple TERT (TERT\u2013NUBPL, MARCH6\u2013TERT, and CJD4\u2013TERT) and FGFR2 (CXCL17\u2013FGFR2, SIPA1L3\u2013FGFR2, FGFR2\u2013SIPA1L3, and FGFR2\u2013CEACAM1) gene fusions. After the surgery, the patient\u2019s condition deteriorated rapidly due to the malignant nature of the tumor and she died with an overall survival of 3 months. Our report provides the molecular clue for a novel telomerase activation and maintenance mechanism in GBM.<\/jats:p>","DOI":"10.3389\/fonc.2021.739309","type":"journal-article","created":{"date-parts":[[2021,12,16]],"date-time":"2021-12-16T18:30:07Z","timestamp":1639679407000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Case Report: Identification of Multiple TERT and FGFR2 Gene Fusions in a Pineal Region Glioblastoma Case"],"prefix":"10.3389","volume":"11","author":[{"given":"Xing","family":"Guo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teng","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiming","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao","family":"Song","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dezhi","family":"Shan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shujun","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuo","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,12,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdz164","article-title":"Molecular Pathology of Tumors of the Central Nervous System","volume":"30","author":"Kristensen","year":"2019","journal-title":"Ann Oncol Off J Eur Soc Med Oncol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/now277","article-title":"A Clinical Perspective on the 2016 WHO Brain Tumor Classification and Routine Molecular Diagnostics","volume":"19","author":"van den Bent","year":"2017","journal-title":"Neuro-Oncology"},{"key":"B3","doi-asserted-by":"publisher","first-page":"2087","DOI":"10.1038\/s41467-018-04448-6","article-title":"The Genomic Landscape of TERT Promoter Wildtype-IDH Wildtype Glioblastoma","volume":"9","author":"Diplas","year":"2018","journal-title":"Nat Commun"},{"key":"B4","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1016\/j.ccell.2018.08.003","article-title":"Disruption of the Beta1l Isoform of GABP Reverses Glioblastoma Replicative Immortality in a TERT Promoter Mutation-Dependent Manner","volume":"34","author":"Mancini","year":"2018","journal-title":"Cancer Cell"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-020-0471-6","article-title":"Programmable Base Editing of Mutated TERT Promoter Inhibits Brain Tumour Growth","volume":"22","author":"Li","year":"2020","journal-title":"Nat Cell Biol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/nature25171","article-title":"A Metabolic Function of FGFR3-TACC3 Gene Fusions in Cancer","volume":"553","author":"Frattini","year":"2018","journal-title":"Nature"},{"key":"B7","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1186\/s40478-019-0721-7","article-title":"Coexisting FGFR3 P.K650T Mutation in Two FGFR3-TACC3 Fusion Glioma Cases","volume":"7","author":"Ballester","year":"2019","journal-title":"Acta Neuropathologica Commun"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/now240","article-title":"FGFR-TACC Gene Fusions in Human Glioma","volume":"19","author":"Lasorella","year":"2017","journal-title":"Neuro-Oncology"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-14-2199","article-title":"Detection, Characterization, and Inhibition of FGFR-TACC Fusions in IDH Wild-Type Glioma","volume":"21","author":"Di Stefano","year":"2015","journal-title":"Clin Cancer Res"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuchi.2014.01.005","article-title":"Incidence of Pineal Tumours. 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