Diffuse midline glioma with novel, potentially targetable, FGFR2–VPS35 fusion
- George Zanazzi1,2,
- Benjamin L. Liechty1,3,
- Danielle Pendrick1,
- Olga Krasnozhen-Ratush4,5,
- Matija Snuderl4,
- Jeffrey C. Allen6,
- James H. Garvin7,
- Mahesh M. Mansukhani1,
- Kevin A. Roth1 and
- Susan J. Hsiao1
- 1Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York 10032, USA;
- 2Department of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire 03766, USA;
- 3Department of Pathology, Weill Cornell Medical College, New York, New York 10021, USA;
- 4Department of Pathology, NYU Langone Medical Center, New York, New York, 10016, USA;
- 5Department of Pathology, Baystate Medical Center, Springfield, Massachusetts 01199, USA;
- 6Department of Pediatrics, NYU Langone Medical Center, New York, New York 10016, USA;
- 7Department of Pediatrics, Columbia University Irving Medical Center, New York, New York 10032, USA
- Corresponding author: george.j.zanazzi{at}hitchcock.org
Abstract
We report a case of a slow-growing, diffuse, infiltrating glioma in the right brainstem of a 9-yr-old boy. The tumor was negative by immunohistochemical staining for histone H3 K27M, BRAF V600E, and IDH1 R132H mutations. Fluorescence in situ hybridization did not reveal a BRAF duplication. Genomic profiling of the tumor, by DNA methylation array and cancer whole-exome and transcriptome sequencing, was performed. This analysis showed copy-number alterations, including gains of several chromosomes. In addition, a novel fusion involving the first 17 exons of FGFR2 fused to exon 2 of VPS35 was identified. This novel fusion is predicted to result in activation of fibroblast growth factor receptor (FGFR) signaling and is potentially targetable using FGFR inhibitors. This tumor expands the spectrum of pediatric diffuse gliomas.
Footnotes
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[Supplemental material is available for this article.]
- Received June 10, 2020.
- Accepted August 19, 2020.
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