Comprehensive analysis of diverse low-grade neuroepithelial tumors with FGFR1 alterations reveals a distinct molecular signature of rosette-forming glioneuronal tumor.

Autor:	Lucas CG; Division of Neuropathology, Department of Pathology, University of California, San Francisco, 513 Parnassus Avenue, Health Sciences West 451, San Francisco, CA, 94143, USA., Gupta R; Division of Neuropathology, Department of Pathology, University of California, San Francisco, 513 Parnassus Avenue, Health Sciences West 451, San Francisco, CA, 94143, USA., Doo P; Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA., Lee JC; Division of Neuropathology, Department of Pathology, University of California, San Francisco, 513 Parnassus Avenue, Health Sciences West 451, San Francisco, CA, 94143, USA., Cadwell CR; Division of Neuropathology, Department of Pathology, University of California, San Francisco, 513 Parnassus Avenue, Health Sciences West 451, San Francisco, CA, 94143, USA., Ramani B; Division of Neuropathology, Department of Pathology, University of California, San Francisco, 513 Parnassus Avenue, Health Sciences West 451, San Francisco, CA, 94143, USA., Hofmann JW; Division of Neuropathology, Department of Pathology, University of California, San Francisco, 513 Parnassus Avenue, Health Sciences West 451, San Francisco, CA, 94143, USA., Sloan EA; Division of Neuropathology, Department of Pathology, University of California, San Francisco, 513 Parnassus Avenue, Health Sciences West 451, San Francisco, CA, 94143, USA., Kleinschmidt-DeMasters BK; Departments of Pathology, Neurology, and Neurosurgery, University of Colorado, Aurora, CO, USA., Lee HS; Department of Pathology, Sutter Medical Center, Sacramento, CA, USA., Wood MD; Department of Pathology, Oregon Health & Science University, Portland, OR, USA., Grafe M; Department of Pathology, Oregon Health & Science University, Portland, OR, USA., Born D; Division of Neuropathology, Department of Pathology, Stanford University, Palo Alto, CA, USA., Vogel H; Division of Neuropathology, Department of Pathology, Stanford University, Palo Alto, CA, USA., Salamat S; Department of Anatomic Pathology, University of Wisconsin-Madison, Madison, WI, USA., Puccetti D; Division of Hematology, Oncology, and Bone Marrow Transplant, Department of Pediatrics, University of Wisconsin-Madison, Madison, WI, USA., Scharnhorst D; Department of Pathology, Valley Children's Hospital, Madera, CA, USA., Samuel D; Department of Hematology/Oncology, Valley Children's Hospital, Madera, CA, USA., Cooney T; Department of Pediatric Oncology, Dana Farber Cancer Institute, Boston, MA, USA., Cham E; Department of Pathology, UCSF Benioff Children's Hospital Oakland, Oakland, CA, USA., Jin LW; Department of Pathology, University of California, Davis, Sacramento, CA, USA., Khatib Z; Division of Pediatric Hematology/Oncology, Department of Pediatrics, Nicklaus Children's Hospital, Miami, FL, USA., Maher O; Division of Pediatric Hematology/Oncology, Department of Pediatrics, Nicklaus Children's Hospital, Miami, FL, USA., Chamyan G; Department of Pathology, Nicklaus Children's Hospital, Miami, FL, USA., Brathwaite C; Department of Pathology, Nicklaus Children's Hospital, Miami, FL, USA., Bannykh S; Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, CA, USA., Mueller S; Division of Pediatric Hematology/Oncology, Department of Pediatrics, University of California, San Francisco, San Francisco, CA, USA.; Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.; Division of Neuro-Oncology, Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA., Kline CN; Division of Pediatric Hematology/Oncology, Department of Pediatrics, University of California, San Francisco, San Francisco, CA, USA.; Department of Neurology, University of California, San Francisco, San Francisco, CA, USA., Banerjee A; Division of Pediatric Hematology/Oncology, Department of Pediatrics, University of California, San Francisco, San Francisco, CA, USA., Reddy A; Division of Pediatric Hematology/Oncology, Department of Pediatrics, University of California, San Francisco, San Francisco, CA, USA.; Department of Neurology, University of California, San Francisco, San Francisco, CA, USA., Taylor JW; Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.; Division of Neuro-Oncology, Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA., Clarke JL; Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.; Division of Neuro-Oncology, Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA., Oberheim Bush NA; Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.; Division of Neuro-Oncology, Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA., Butowski N; Division of Neuro-Oncology, Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA., Gupta N; Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA., Auguste KI; Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA., Sun PP; Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA., Roland JL; Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA., Raffel C; Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA., Aghi MK; Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA., Theodosopoulos P; Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA., Chang E; Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA., Hervey-Jumper S; Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA., Phillips JJ; Division of Neuropathology, Department of Pathology, University of California, San Francisco, 513 Parnassus Avenue, Health Sciences West 451, San Francisco, CA, 94143, USA.; Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA., Pekmezci M; Division of Neuropathology, Department of Pathology, University of California, San Francisco, 513 Parnassus Avenue, Health Sciences West 451, San Francisco, CA, 94143, USA., Bollen AW; Division of Neuropathology, Department of Pathology, University of California, San Francisco, 513 Parnassus Avenue, Health Sciences West 451, San Francisco, CA, 94143, USA., Tihan T; Division of Neuropathology, Department of Pathology, University of California, San Francisco, 513 Parnassus Avenue, Health Sciences West 451, San Francisco, CA, 94143, USA., Chang S; Division of Neuro-Oncology, Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA., Berger MS; Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA., Perry A; Division of Neuropathology, Department of Pathology, University of California, San Francisco, 513 Parnassus Avenue, Health Sciences West 451, San Francisco, CA, 94143, USA.; Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA., Solomon DA; Division of Neuropathology, Department of Pathology, University of California, San Francisco, 513 Parnassus Avenue, Health Sciences West 451, San Francisco, CA, 94143, USA. david.solomon@ucsf.edu.
Jazyk:	angličtina
Zdroj:	Acta neuropathologica communications [Acta Neuropathol Commun] 2020 Aug 28; Vol. 8 (1), pp. 151. Date of Electronic Publication: 2020 Aug 28.
DOI:	10.1186/s40478-020-01027-z
Abstrakt:	The FGFR1 gene encoding fibroblast growth factor receptor 1 has emerged as a frequently altered oncogene in the pathogenesis of multiple low-grade neuroepithelial tumor (LGNET) subtypes including pilocytic astrocytoma, dysembryoplastic neuroepithelial tumor (DNT), rosette-forming glioneuronal tumor (RGNT), and extraventricular neurocytoma (EVN). These activating FGFR1 alterations in LGNET can include tandem duplication of the exons encoding the intracellular tyrosine kinase domain, in-frame gene fusions most often with TACC1 as the partner, or hotspot missense mutations within the tyrosine kinase domain (either at p.N546 or p.K656). However, the specificity of these different FGFR1 events for the various LGNET subtypes and accompanying genetic alterations are not well defined. Here we performed comprehensive genomic and epigenomic characterization on a diverse cohort of 30 LGNET with FGFR1 alterations. We identified that RGNT harbors a distinct epigenetic signature compared to other LGNET with FGFR1 alterations, and is uniquely characterized by FGFR1 kinase domain hotspot missense mutations in combination with either PIK3CA or PIK3R1 mutation, often with accompanying NF1 or PTPN11 mutation. In contrast, EVN harbors its own distinct epigenetic signature and is characterized by FGFR1-TACC1 fusion as the solitary pathogenic alteration. Additionally, DNT and pilocytic astrocytoma are characterized by either kinase domain tandem duplication or hotspot missense mutations, occasionally with accompanying NF1 or PTPN11 mutation, but lacking the accompanying PIK3CA or PIK3R1 mutation that characterizes RGNT. The glial component of LGNET with FGFR1 alterations typically has a predominantly oligodendroglial morphology, and many of the pilocytic astrocytomas with FGFR1 alterations lack the biphasic pattern, piloid processes, and Rosenthal fibers that characterize pilocytic astrocytomas with BRAF mutation or fusion. Together, this analysis improves the classification and histopathologic stratification of LGNET with FGFR1 alterations.
Databáze:	MEDLINE
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