Journal Article

PATH-11. DESIGNING A DIAGNOSTIC FGFR3-TACC3 FUSION ASSAY USING RT-PCR FOR GLIOBLASTOMA MULTIFORME PATIENTS

Wendy de Leng, Anne Hoskam, Joyce van Kuik, Wim Spliet, Wim Van Hecke, Pierre Robe and Filip de Vos

in Neuro-Oncology

Volume 19, issue suppl_6, pages vi172-vi173
Published in print November 2017 | ISSN: 1522-8517
Published online November 2017 | e-ISSN: 1523-5866 | DOI: https://dx.doi.org/10.1093/neuonc/nox168.702
PATH-11. DESIGNING A DIAGNOSTIC FGFR3-TACC3 FUSION ASSAY USING RT-PCR FOR GLIOBLASTOMA MULTIFORME PATIENTS

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Abstract

The FGFR3-TACC3 fusion protein is a recurrent translocation in glioblastoma (GBM) patients and other types of solid malignancies, and is hypothesized to confer oncogenic transformation. Preliminary evidence of FGFR3 tyrosine kinase inhibitor (TKI) therapy has shown significant effectivity in vitro, in vivo and in phase I clinical trials, validating FGFR as a potential therapeutic target. A screening assay for the FGFR3-TACC3 translocation can thus be of great value for GBM patients, a patient population that currently lacks effective therapeutic interventions. An RT-PCR assay was designed to detect the FGFR3-TACC3 fusion gene transcripts in FFPE tissue from archival glioma samples. FGFR3 N-terminal immunostaining preselection was performed to identify potential FGFR3-TACC3 fusion positive gliomas. Out of 467 gliomas, 14 (of which13 GBM) samples showed FGFR3 overexpression. Out of these 14, 12 were available for further RT-PCR analysis, revealing 7 FGFR3-TACC3 positive cases. All 7 cases were validated on FFPE, whereas 5/7 were validated on fresh frozen material, together revealing three of the most frequently observed fusion variants; FGFR3ex17-TACC3ex11, FGFR3ex17-TACC3ex8, and FGFR3ex17-TACC3ex10. The remaining FGFR3 immunopositive but FGFR3-TACC3 negative cases were analyzed by FISH, which revealed no FGFR3 amplification. In conclusion, this study is the first to validate an FFPE tissue based RT-PCR screening method for the FGFR3-TACC3 translocation, thereby contributing to personalized cancer treatment of glioma patients.

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Subjects: Medical Oncology ; Neurology

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