Objective:

To introduce a newly identified fusion, GNAI2::BRAF, as the oncogenic driver in a rare case of adult pilocytic astrocytoma 

Background:

Pilocytic astrocytoma is a circumscribed astrocytic glioma that primarily affects children and young adults. These tumors are driven by alterations in the MAPK pathway, most commonly the KIAA1549::BRAF fusion, BRAF V600E mutation, and NF1 mutation. Other activating fusions involving BRAF have also rarely been reported.  

Design/Methods:

Case Report.

Results:

We present the case of a 58-year-old right-handed female who presented with transient right forearm and paresthesia. MRI brain with and without contrast revealed a 1.4 cm non-enhancing T2 hyperintense lesion in the left frontal lobe. She underwent surgical resection. Histology showed a low-grade glial neoplasm with Rosenthal fibers. Initial molecular testing was negative for the KIAA1549::BRAF fusion, though RNA fusion analysis using a partner agnostic assay showed a GNAI2::BRAF fusion, which has not been previously reported. Methylation profiling by both the Heidelberg and NCI/Bethesda classifiers indicated a consensus match with supratentorial pilocytic astrocytoma. The patient had a gross total surgical resection, is clinically asymptomatic, and is being monitored by surveillance MRIs. Analysis of RNA sequencing data from a large cohort of low-grade glial tumors from our institution is in process to determine how common this fusion is. 

Conclusions:

This case establishes GNAI2::BRAF as a rare oncogenic driver in pilocytic astrocytoma. Novel molecular pathology methods including a partner agnostic RNA fusion assay and methylome profiling were central to establishing this diagnosis.