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Published on: August 25, 2021
A novel BRAF::PTPRN2 fusion in meningioma: a case report
Nishanth S Sadagopan1, Khizar R Nandoliya1, Mark W Youngblood1
1Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, 676 N. St. Clair Street, Suite 2210, Chicago, IL, 60611, USA.
Abstract:
Gene fusion events have been linked to oncogenesis in many cancers. However, gene fusions in meningioma are understudied compared to somatic mutations, chromosomal gains/losses, and epigenetic changes. Fusions involving B-raf proto-oncogene, serine/threonine kinase (BRAF) are subtypes of oncogenic BRAF genetic abnormalities that have been reported in certain cases of brain tumors, such as pilocytic astrocytomas. However, BRAF fusions have not been recognized in meningioma. We present the case of an adult female presenting with episodic partial seizures characterized by déjà vu, confusion, and cognitive changes. Brain imaging revealed a cavernous sinus and sphenoid wing mass and she underwent resection. Histopathology revealed a World Health Organization (WHO) grade 1 meningioma. Genetic profiling with next generation sequencing and microarray analysis revealed an in-frame BRAF::PTPRN2 fusion affecting the BRAF kinase domain as well as chromothripsis of chromosome 7q resulting in multiple segmental gains and losses including amplifications of cyclin dependent kinase 6 (CDK6), tyrosine protein-kinase Met (MET), and smoothened (SMO). Elevated pERK staining in tumor cells provided evidence of activated mitogen-activated protein kinase (MAPK) signaling. This report raises the possibility that gene fusion events may be involved in meningioma pathogenesis and warrant further investigation.
Insights
This study identified a novel BRAF::PTPRN2 gene fusion in a meningioma case, suggesting gene fusions may contribute to meningioma development. Further research is needed to explore this finding in meningioma pathogenesis.
Area of Science:
- Neuro-oncology
- Cancer Genomics
- Molecular Pathology
Background:
- Gene fusions are implicated in various cancers but are understudied in meningioma compared to other genetic alterations.
- BRAF fusions are known oncogenic drivers in some brain tumors but have not been previously reported in meningioma.
Observation:
- A case of a WHO grade 1 meningioma in an adult female with seizures and a sphenoid wing mass was analyzed.
- Genetic profiling revealed an in-frame BRAF::PTPRN2 fusion and chromothripsis on chromosome 7q, leading to amplifications of CDK6, MET, and SMO.
Findings:
- The identified BRAF::PTPRN2 fusion affects the BRAF kinase domain.
- Elevated pERK staining indicated activation of the mitogen-activated protein kinase (MAPK) signaling pathway.
- Chromothripsis resulted in segmental chromosomal gains and losses, including amplifications of key oncogenes.
Implications:
- This case suggests that gene fusions, specifically BRAF fusions, may play a role in meningioma pathogenesis.
- The findings highlight the need for further investigation into gene fusion events in meningioma development.
- Understanding these genetic alterations could lead to new diagnostic and therapeutic strategies for meningioma.
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