{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T23:41:01Z","timestamp":1789947661840,"version":"4.0.1"},"reference-count":20,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2020,12,2]],"date-time":"2020-12-02T00:00:00Z","timestamp":1606867200000},"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>\n                    Central nervous system (CNS) embryonal tumors (WHO grade IV) are a heterogeneous group of rare, poorly differentiated neuroepithelial malignant neoplasms that commonly occur in children, and they have a poor prognosis. The 2016 WHO (World Health Organization) classification of CNS tumors created a major shift in paradigm of the classification of embryonal tumors. However, some cases were still difficult to classify. Further integrative genomic analysis is needed to improve the precise classification, diagnosis and treatment of CNS embryonal tumors. Herein, we firstly report a case of CNS embryonal tumor harboring the pathogenic\n                    <jats:italic>CIC<\/jats:italic>\n                    \u2013\n                    <jats:italic>LEUTX<\/jats:italic>\n                    gene fusion. A 2-year-old male infant presented with a solid cystic mass in the left temporal lobe-basal ganglia and left parietal lobe (maximum diameter, 75 mm) and underwent gross tumor resection. The tumor was classified as a poorly differentiated embryonal neoplasm of neuroectodermal origin that lacked specific features and rosettes. By immunohistochemistry, the tumor cells were strongly positive for synaptophysin, and the Ki67 proliferation index was high (&amp;gt;50%). FISH (Fluorescence in situ hybridization) results indicated no change in the copy number at the 19q13.42 C19MC locus. Next generation sequencing showed a\n                    <jats:italic>CIC<\/jats:italic>\n                    \u2013\n                    <jats:italic>LEUTX<\/jats:italic>\n                    gene fusion, a somatic\n                    <jats:italic>TSC2<\/jats:italic>\n                    c.G2714A mutation, and a heterozygous germline\n                    <jats:italic>NBN<\/jats:italic>\n                    c.C127T\u00a0mutation. One month after surgery, there was recurrence of the intracranial tumor (maximum diameter, 55 mm) as well as spinal cord implantation metastasis. The patient received chemotherapy (CTX+CBP+VCR\/DDP+VP-16), radiotherapy, and a drug targeting the\n                    <jats:italic>TSC2<\/jats:italic>\n                    gene (everolimus). At the time of this writing, the patient is alive without evidence of disease for 11 months. This is the first report of the\n                    <jats:italic>CIC<\/jats:italic>\n                    \u2013\n                    <jats:italic>LEUTX<\/jats:italic>\n                    gene fusion in a case of CNS embryonal tumor.\n                  <\/jats:p>","DOI":"10.3389\/fonc.2020.598970","type":"journal-article","created":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T23:37:28Z","timestamp":1606865848000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":25,"title":["Case Report: A Unique Case of Pediatric Central Nervous System Embryonal Tumor Harboring the CIC\u2013LEUTX Fusion, Germline NBN Variant and Somatic TSC2 Mutation: Expanding the Spectrum of CIC-Rearranged Neoplasia"],"prefix":"10.3389","volume":"10","author":[{"given":"Wanming","family":"Hu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhang","family":"Ji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofei","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2020,12,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-020-02182-2","article-title":"ETMR: a tumor entity in its infancy","volume":"140","author":"Lambo","year":"2020","journal-title":"Acta Neuropathol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-018-1808-0","article-title":"cIMPACT-NOW update 1: Not otherwise specified (NOS) and not elsewhere classified (NEC)","volume":"135","author":"Louis","year":"2018","journal-title":"Acta Neuropathol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-0895-y","article-title":"PKG1-modified TSC2 regulates mTORC1 activity to counter adverse cardiac stress","volume":"566","author":"Ranek","year":"2019","journal-title":"Nature"},{"key":"B4","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1080\/15384047.2019.1665955","article-title":"Two novel TSC2 mutations in renal epithelioid angiomyolipoma sensitive to everolimus","volume":"21","author":"Wang","year":"2020","journal-title":"Cancer Biol 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nervous system angiosarcoma with CIC-LEUTX gene rearrangement (P3. 6-017)","volume":"92","author":"Noch","year":"2019","journal-title":"Neurology"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2015.5699","article-title":"Diagnostic yield of clinical tumor and germline whole-exome sequencing for children with solid tumors","volume":"2","author":"Parsons","year":"2016","journal-title":"JAMA Oncol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.humpath.2018.12.006","article-title":"New fusion sarcomas: histopathology and clinical significance of selected entities","volume":"86","author":"Miettinen","year":"2019","journal-title":"Hum Pathol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-019-02720-8","article-title":"Ewing sarcoma and Ewing-like tumors","volume":"476","author":"Sbaraglia","year":"2020","journal-title":"Virchows 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PRD-like homeobox gene LEUTX has a central role in embryo genome activation","volume":"143","author":"Jouhilahti","year":"2016","journal-title":"Development"},{"key":"B16","doi-asserted-by":"publisher","first-page":"e28663","DOI":"10.1002\/pbc.28663","article-title":"Rapidly progressing acute myeloid leukemia with KAT6A-LEUTX fusion in a newborn","author":"Sramkova","year":"2020","journal-title":"Pediatr Blood Cancer"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-16-3351","article-title":"CIC-DUX4 Induces Small Round Cell Sarcomas Distinct from Ewing Sarcoma","volume":"77","author":"Yamazaki","year":"2017","journal-title":"Cancer Res"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1172\/JCI126366","article-title":"CIC-DUX4 oncoprotein drives sarcoma metastasis and tumorigenesis via distinct regulatory programs","volume":"129","author":"Okimoto","year":"2019","journal-title":"J Clin 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