Molecular Profiling of a Rare Rosette-Forming Glioneuronal Tumor Arising in the Spinal Cord

send to a friend share this

Molecular Profiling of a Rare Rosette-Forming Glioneuronal Tumor Arising in the Spinal Cord

Thursday, 24.09.2015

Authors and Affiliations:

Lucas Tadeu Bidinotto1,2, Cristovam Scapulatempo-Neto1,3*, Alan Mackay4, Gisele Caravina de Almeida3, Bernd Walter Scheithauer5, Gustavo Noriz Berardinelli1, Raul Torrieri1, Carlos Afonso Clara6, Leonir Terezinha Feltrin7, Marta Viana-Pereira8,9, Marileila Varella-Garcia10, Chris Jones4, Rui Manuel Reis1,8,9*.

1Molecular OncologyResearch Center, Barretos Cancer Hospital, Barretos, SP, Brazil

2Barretos Schoolof Health Sciences, Dr. Paulo Prata - FACISB, Barretos, SP, Brazil

3Department of Pathology, Barretos Cancer Hospital, Barretos, SP, Brazil

4Divisions of Molecular Pathology and Cancer Therapeutics, Institute for Cancer Research, London, Surrey, United Kingdom

5Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, United States of America

6Department of Neurosurgery, Barretos Cancer Hospital,Barretos, SP, Brazil

7Department of Radiology, Barretos Cancer Hospital,Barretos, SP, Brazil

8Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal

93B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal

10University of Colorado Anschutz Medical Campus | Medical Oncology/Departmentof Medicine, Aurora, Colorado, United States of America



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, with typical characteristics of 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, driver by KIAA1549:BRAF fusion and MLL2 mutation, respectively, could be associated with the development of this rare tumor entity.


Journal: Plos One