Case Report: Next generation sequencing identifies a NAB2-STAT6 fusion in Glioblastoma

Diagnostic Pathology
Phedias DiamandisShakti H Ramkissoon

Abstract

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. 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 de...Continue Reading

References

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Citations

Jun 24, 2017·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Phedias Diamandis, Kenneth D Aldape
Oct 3, 2017·International Journal of Gynecological Pathology : Official Journal of the International Society of Gynecological Pathologists·Juan C TardíoAntonio Llombart-Bosch

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Methods Mentioned

BETA
exome sequencing
nuclear translocation

Software Mentioned

OncoPanel

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