title: Case Report: Next generation sequencing identifies a NAB2-STAT6 fusion in Glioblastoma.
abstract: BACKGROUND
  Molecular profiling has uncovered genetic subtypes of glioblastoma (GBM), including tumors with IDH1 mutations that confer increase survival and improved response to standard-of-care therapies.  By mapping the genetic landscape of brain tumors in routine clinical practice, we enable rapid identification of targetable genetic alterations.
  
  
  METHODS
  A 29-year-old male presented with new onset seizures prompting neuroimaging studies, which revealed an enhancing 5 cm intra-axial lesion involving the right parietal lobe. He underwent a subtotal resection and pathologic examination revealed glioblastoma with mitoses, microvascular proliferation and necrosis. Immunohistochemical (IHC) analysis showed diffuse expression of GFAP, OLIG2 and SOX2 consistent with a tumor of glial lineage. Tumor cells were positive for IDH1(R132H) and negative for ATRX. Clinical targeted-exome sequencing (DFBWCC Oncopanel) identified multiple functional variants including IDH1 (p.R132H), TP53 (p.Y126_splice), ATRX (p.R1302fs*), HNF1A (p.R263H) and NF1 (p.H2592del) variants and a NAB2-STAT6 gene fusion event involving NAB2 exon 3 and STAT6 exon 18. Array comparative genomic hybridization (aCGH) further revealed a focal amplification of NAB2 and STAT6.  IHC analysis demonstrated strong heterogenous STAT6 nuclear localization (in 20 % of tumor cells).
  
  
  CONCLUSIONS
  While NAB2:STAT6 fusions are common in solitary fibrous tumors (SFT), we report this event for the first time in a newly diagnosed, secondary-type GBM or any other non-SFT. Our study further highlights the value of comprehensive genomic analyses in identifying patient-specific targetable mutations and rearrangements.
authors.affiliation: Neuropathology Program, Department of Laboratory Medicine and Pathobiology, University of Toronto, 27 King's College Circle, Toronto, ON, M5S, Canada. p.diamandis@mail.utoronto.ca.|Department of Pathology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA, 02115, USA. p.diamandis@mail.utoronto.ca.
authors.forename: Phedias
authors.initials: P
authors.lastname: Diamandis
authors.affiliation: Cancer Program, Broad Institute of MIT and Harvard, 415 Main St, Cambridge, MA, 02142, USA. rferrer@broadinstitute.org.|Department of Cancer Biology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA, 02115, USA. rferrer@broadinstitute.org.
authors.forename: Ruben
authors.initials: R
authors.lastname: Ferrer-Luna
authors.affiliation: Department of Radiology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA, 02115, USA. ryhuang@partners.org.
authors.forename: Raymond Y
authors.initials: RY
authors.lastname: Huang
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA, 02115, USA. rfolkerth@partners.org.|Department of Pathology, Harvard Medical School, 25 Shattuck Street, Boston, MA, 02115, USA. rfolkerth@partners.org.|Department of Pathology, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, 02115, USA. rfolkerth@partners.org.
authors.forename: Rebecca D
authors.initials: RD
authors.lastname: Folkerth
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA, 02115, USA. aligon@partners.org.|Department of Pathology, Harvard Medical School, 25 Shattuck Street, Boston, MA, 02115, USA. aligon@partners.org.
authors.forename: Azra H
authors.initials: AH
authors.lastname: Ligon
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA, 02115, USA. Patrick_Wen@dfci.harvard.edu.
authors.forename: Patrick Y
authors.initials: PY
authors.lastname: Wen
authors.affiliation: Cancer Program, Broad Institute of MIT and Harvard, 415 Main St, Cambridge, MA, 02142, USA. Rameen_Beroukhim@dfci.harvard.edu.|Department of Cancer Biology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA, 02115, USA. Rameen_Beroukhim@dfci.harvard.edu.
authors.forename: Rameen
authors.initials: R
authors.lastname: Beroukhim
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA, 02115, USA. Keith_Ligon@dfci.harvard.edu.|Cancer Program, Broad Institute of MIT and Harvard, 415 Main St, Cambridge, MA, 02142, USA. Keith_Ligon@dfci.harvard.edu.|Department of Pathology, Harvard Medical School, 25 Shattuck Street, Boston, MA, 02115, USA. Keith_Ligon@dfci.harvard.edu.|Department of Pathology, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, 02115, USA. Keith_Ligon@dfci.harvard.edu.|Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA, 02115, USA. Keith_Ligon@dfci.harvard.edu.
authors.forename: Keith L
authors.initials: KL
authors.lastname: Ligon
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA, 02115, USA. sramkissoon@partners.org.|Department of Pathology, Harvard Medical School, 25 Shattuck Street, Boston, MA, 02115, USA. sramkissoon@partners.org.|Department of Pathology, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, 02115, USA. sramkissoon@partners.org.|Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA, 02115, USA. sramkissoon@partners.org.
authors.forename: Shakti H
authors.initials: SH
authors.lastname: Ramkissoon
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics*; D001932:Brain Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D055028:Comparative Genomic Hybridization; D050939:Gene Fusion; D020022:Genetic Predisposition to Disease; D005909:Glioblastoma / Q000737:chemistry / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D008297:Male; D010296:Parietal Lobe / Q000737:chemistry / Q000473:pathology / Q000601:surgery; D010641:Phenotype; D011237:Predictive Value of Tests; D012097:Repressor Proteins / Q000235:genetics*; D050800:STAT6 Transcription Factor / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C491000:NAB2 protein, human; D012097:Repressor Proteins; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human
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