title: Molecular Profiling of a Rare Rosette-Forming Glioneuronal Tumor Arising in the Spinal Cord.
abstract: Rosette-forming glioneuronal tumor (RGNT) of the IV ventricle is a rare and recently recognized brain tumor entity. It is histologically composed by two distinct features: a glial component, resembling pilocytic astrocytoma, and a component forming neurocytic rosettes and/or perivascular rosettes. Herein, we describe a 33-year-old man with RGNT arising in the spinal cord. Following an immunohistochemistry validation, we further performed an extensive genomic analysis, using array-CGH (aCGH), whole exome and cancer-related hotspot sequencing, in order to better understand its underlying biology. We observed the loss of 1p and gain of 1q, as well as gain of the whole chromosomes 7, 9 and 16. Local amplifications in 9q34.2 and 19p13.3 (encompassing the gene SBNO2) were identified. Moreover, we observed focal gains/losses in several chromosomes. Additionally, on chromosome 7, we identified the presence of the KIAA1549:BRAF gene fusion, which was further validated by RT-PCR and FISH. Across all mutational analyses, we detected and validated the somatic mutations of the genes MLL2, CNNM3, PCDHGC4 and SCN1A. Our comprehensive molecular profiling of this RGNT suggests that MAPK pathway and methylome changes, driven by KIAA1549:BRAF fusion and MLL2 mutation, respectively, could be associated with the development of this rare tumor entity.
authors.affiliation: Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, SP, Brazil; Barretos School of Health Sciences, Dr. Paulo Prata-FACISB, Barretos, SP, Brazil.
authors.forename: Lucas Tadeu
authors.initials: LT
authors.lastname: Bidinotto
authors.affiliation: Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, SP, Brazil; Department of Pathology, Barretos Cancer Hospital, Barretos, SP, Brazil.
authors.forename: Cristovam
authors.initials: C
authors.lastname: Scapulatempo-Neto
authors.affiliation: Divisions of Molecular Pathology and Cancer Therapeutics, Institute for Cancer Research, London, Surrey, United Kingdom.
authors.forename: Alan
authors.initials: A
authors.lastname: Mackay
authors.affiliation: Department of Pathology, Barretos Cancer Hospital, Barretos, SP, Brazil.
authors.forename: Gisele Caravina
authors.initials: GC
authors.lastname: de Almeida
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, United States of America.
authors.forename: Bernd Walter
authors.initials: BW
authors.lastname: Scheithauer
authors.affiliation: Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, SP, Brazil.
authors.forename: Gustavo Noriz
authors.initials: GN
authors.lastname: Berardinelli
authors.affiliation: Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, SP, Brazil.
authors.forename: Raul
authors.initials: R
authors.lastname: Torrieri
authors.affiliation: Department of Neurosurgery, Barretos Cancer Hospital, Barretos, SP, Brazil.
authors.forename: Carlos Afonso
authors.initials: CA
authors.lastname: Clara
authors.affiliation: Department of Radiology, Barretos Cancer Hospital, Barretos, SP, Brazil.
authors.forename: Leonir Terezinha
authors.initials: LT
authors.lastname: Feltrin
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal; 3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: Marta
authors.initials: M
authors.lastname: Viana-Pereira
authors.affiliation: University of Colorado Anschutz Medical Campus, Medical Oncology/Department of Medicine, Aurora, Colorado, United States of America.
authors.forename: Marileila
authors.initials: M
authors.lastname: Varella-Garcia
authors.affiliation: Divisions of Molecular Pathology and Cancer Therapeutics, Institute for Cancer Research, London, Surrey, United Kingdom.
authors.forename: Chris
authors.initials: C
authors.lastname: Jones
authors.affiliation: Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, SP, Brazil; Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal; 3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: Rui Manuel
authors.initials: RM
authors.lastname: Reis
mesh_terms: D000328:Adult; D001932:Brain Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D002872:Chromosome Deletion; D059472:Exome / Q000235:genetics; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D013116:Spinal Cord