ArticleBrain pathology (Zurich, Switzerland)2017
Genetic alterations related to BRAF-FGFR genes and dysregulated MAPK/ERK/mTOR signaling in adult pilocytic astrocytoma.
Article in Brain pathology (Zurich, Switzerland), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 33 citations in OpenAlex.
- Concurrence of FGFR1 mutations modulates oncogenesis in glioneuronal tumors.The EMBO journal · 2025Article
- Expanding morphological spectrum of pilocytic astrocytomas: insights from integrated histopathological and multiomic profiling.Journal of neuro-oncology · 2025Article
- A bibliometric analysis of research trends and hotspots of pilocytic astrocytoma from 2004 to 2023.Neurosurgical review · 2024Article
- Clinical and molecular study of radiation-induced gliomas.Scientific reports · 2024Article
- Rare vermian pilocytic astrocytoma with recurrent spontaneous hemorrhage in the elderly: A case report and review of literature.Surgical neurology international · 2024Article
- Detoxified pneumolysin derivative ΔA146Ply inhibits autophagy and induces apoptosis in acute myeloid leukemia cells by activating mTOR signaling.Experimental & molecular medicine · 2022Article
- Typical Pediatric Brain Tumors Occurring in Adults-Differences in Management and Outcome.Biomedicines · 2021Review
- Adult pilocytic astrocytoma in the molecular era: a comprehensive review.CNS oncology · 2021Review
- Recurrent adult pilocytic astrocytoma presenting with intraventricular and leptomeningeal spread.Surgical neurology international · 2021Article
- Comprehensive analysis of diverse low-grade neuroepithelial tumors with FGFR1 alterations reveals a distinct molecular signature of rosette-forming glioneuronal tumor.Acta neuropathologica communications · 2020Article
- Actionable FGFR1 and BRAF mutations in adult circumscribed gliomas.Journal of neuro-oncology · 2019Article
- Pilocytic astrocytomas: BRAFV600E and BRAF fusion expression patterns in pediatric and adult age groups.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2019Article
- CDKN2A/B Loss Is Associated with Anaplastic Transformation in a Case of NTRK2 Fusion-positive Pilocytic Astrocytoma.Neuropathology and applied neurobiology · 2019Article
- Significance of Amphiregulin (AREG) for the Outcome of Low and High Grade Astrocytoma Patients.Journal of Cancer · 2019Article
- Article
- A novel GIT2-BRAF fusion in pilocytic astrocytoma.Diagnostic pathology · 2017Article
- Co-amplification of phosphoinositide 3-kinase enhancer A and cyclin-dependent kinase 4 triggers glioblastoma progression.Oncogene · 2017Article
- Receptor tyrosine kinases play a significant role in human oligodendrocyte inflammation and cell death associated with the Lyme disease bacterium Borrelia burgdorferi.Journal of neuroinflammation · 2017Article
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9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pilocytic astrocytomas occur rarely in adults and show aggressive tumor behavior. However, their underlying molecular-genetic events are largely uncharacterized. Hence, 59 adult pilocytic astrocytoma (APA) cases of classical histology were studied (MIB-1 LI: 1%-5%). Analysis of BRAF alterations using qRT-PCR, confirmed KIAA1549-BRAF fusion in 11 (19%) and BRAF-gain in 2 (3.4%) cases. BRAF-V600E mutation was noted in 1 (1.7%) case by sequencing. FGFR1-mutation and FGFR-TKD duplication were seen in 7/59 (11.9%) and 3/59 (5%) cases, respectively. Overall 36% of APAs harbored BRAF and/or FGFR genetic alterations. Notably, FGFR related genetic alterations were enriched in tumors of supratentorial region (8/25, 32%) as compared with other locations (P = 0.01). The difference in age of cases with FGFR1-mutation (Mean age ± SD: 37.2 ± 15 years) vs. KIAA1549-BRAF fusion (Mean age ± SD: 25.1 ± 4.1 years) was statistically significant (P = 0.03). Combined BRAF and FGFR alterations were identified in 3 (5%) cases. Notably, the cases with more than one genetic alteration were in higher age group (Mean age ± SD: 50 ± 12 years) as compared with cases with single genetic alteration (Mean age ± SD: 29 ± 10; P = 0.003). Immunopositivity of p-MAPK/p-MEK1 was found in all the cases examined. The pS6-immunoreactivity, a marker of mTOR activation was observed in 34/39 (87%) cases. Interestingly, cases with BRAF and/or FGFR related alteration showed significantly lower pS6-immunostatining (3/12; 25%) as compared with those with wild-type BRAF and/or FGFR (16/27; 59%) (P = 0.04). Further, analysis of seven IDH wild-type adult diffuse astrocytomas (DA) showed FGFR related genetic alterations in 43% cases. These and previous results suggest that APAs are genetically similar to IDH wild-type adult DAs. APAs harbor infrequent BRAF alterations but more frequent FGFR alterations as compared with pediatric cases. KIAA1549-BRAF fusion inversely correlates with increasing age whereas FGFR1-mutation associates with older age. Activation of MAPK/ERK/mTOR signaling appears to be an important oncogenic event in APAs and may be underlying event of aggressive tumor behavior. The findings provided a rationale for potential therapeutic advantage of targeting MAPK/ERK/mTOR pathway in APAs.
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