Case Report: Next generation sequencing identifies a NAB2-STAT6 fusion in Glioblastoma. Issue 1 (December 2016)

• Record Type: Journal Article
• Authors: Diamandis, Phedias; Ferrer-Luna, Ruben; Huang, Raymond; Folkerth, Rebecca; Ligon, Azra; Wen, Patrick; Beroukhim, Rameen; Ligon, Keith; Ramkissoon, Shakti
• Is Part Of: Diagnostic pathology. Volume 11:Issue 1(2016)
• Page Start: 1
• Page End: 5
• Publication Date: 2016-12
• Subjects: NAB2-STAT6 -- Glioblastoma -- Next generation sequencing; Pathology, Surgical -- Periodicals; 616.0705
• DOI: 10.1186/s13000-016-0455-9
• Languages: English
• ISSNs: 1746-1596

Abstract

Abstract Background Molecular profiling has uncovered genetic subtypes of glioblastoma (GBM), including tumors withIDH1 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. Case Presentation 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 includingIDH1 (p.R132H), TP53 (p.Y126_splice), ATRX (p.R1302fs*), HNF1A (p.R263H) andNF1 (p.H2592del) variants and aNAB2-STAT6 gene fusion event involvingNAB2 exon 3 andSTAT6 exon 18. Array comparative genomic hybridization (aCGH) further revealed a focal amplification ofNAB2 andSTAT6 . IHC analysis demonstrated strong heterogenous STAT6 nuclear localization (in 20 % of tumor cells). Conclusions WhileNAB2: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.