Pilocytic astrocytoma harboring a novel GNAI3-BRAF fusion
Ruihe Lin1, Alicia Kenyon2, Zi-Xuan Wang1
1Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, USA.
Insights
Pilocytic astrocytoma (PA) is a low-grade brain tumor. Next-generation sequencing identified a novel GNAI3-BRAF fusion in a PA case, expanding knowledge of BRAF fusions in tumor development.
Area of Science:
- Neuro-oncology
- Molecular Genetics
- Cancer Research
Background:
- Pilocytic astrocytoma (PA) is a World Health Organization grade 1 central nervous system (CNS) tumor, primarily affecting children and young adults.
- While surgical resection is often curative, residual tumors can persist, necessitating further understanding of PA biology.
- Next-generation sequencing (NGS) has revealed significant molecular alterations in PAs, particularly BRAF alterations.
Observation:
- This report details a case of a young adult with a posterior fossa cerebellar and cerebellopontine angle mass diagnosed as PA.
- Radiological and morphological features were consistent with PA.
- Next-generation sequencing (NGS) was employed to investigate the molecular underpinnings of the tumor.
Findings:
- The study identified a novel GNAI3-BRAF fusion in the pilocytic astrocytoma.
- This fusion results in an in-frame protein incorporating the BRAF kinase domain.
- BRAF alterations, especially fusions like KIAA1549-BRAF, are increasingly recognized as key drivers in PA tumorigenesis.
Implications:
- The discovery of the GNAI3-BRAF fusion expands the spectrum of known BRAF fusions implicated in PA development.
- This finding offers a potential novel molecular signature for PA diagnosis.
- Identifying specific BRAF fusions may pave the way for targeted therapeutic strategies against pilocytic astrocytoma.
Abstract:
Pilocytic astrocytoma (PA), a central nervous system (CNS) World Health Organization grade 1 tumor, is mainly seen in children or young adults aged 5-19. Surgical resection often provides excellent outcomes, but residual tumors may still remain. This low-grade tumor is well recognized for its classic radiological and morphological features; however, some unique molecular findings have been unveiled by the application of next-generation sequencing (NGS). Among the genetic abnormalities identified in this low-grade tumor, increasing evidence indicates that BRAF alterations, especially BRAF fusions, play an essential role in PA tumorigenesis. Among the several fusion partner genes identified in PAs, KIAA1549-BRAF fusion is notably the most common detectable genetic alteration, especially in the cerebellar PAs. Here, we report a case of a young adult patient with a large, right-sided posterior fossa cerebellar and cerebellopontine angle region mass consistent with a PA. Of note, NGS detected a novel GNAI3-BRAF fusion, which results in an in-frame fusion protein containing the kinase domain of BRAF. This finding expands the knowledge of BRAF fusions in the tumorigenesis of PAs, provides an additional molecular signature for diagnosis, and a target for future therapy.
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