Abstract
BACKGROUND
Pediatric low grade gliomas (PLGG) are the most common central nervous system neoplasms in children. These are driven almost exclusively by alterations in the RAS/MAPK pathway. Specifically, alterations in the BRAF gene have emerged as an important target for therapy. This study aimed to identify the frequency of BRAF alterations in a Brazilian cohort of PLGGs.
RESULTS
Forty-one patients diagnosed between 2001 and 2017 had enough FFPE tissue available for analysis. Real-time PCR test (n=35) was used to assess for BRAFV600E mutations, while BRAF fusions were detected by break-apart fluorescence in situ hybridization (n=30). The histologic distribution was as follows: 73% pilocytic astrocytoma, 12% ganglioglioma, 3% diffuse astrocytoma, 5% pleomorphic xanthoastrocytomas (PXA) and 7% NOS (n = 41). BRAF fusions were present in 21 patients (51%): 17 pilocytic astrocytomas, 2 xanthoastrocytoma, 1 pilomyxoid astrocytoma and 1 diffuse astrocytoma. BRAFV600E was detected in 4 cases (10%): 2 pilocytic astrocytomas, 1 ganglioglioma and 1 PXA. As expected, BRAF translocations were more frequent in pilocytic astrocytomas (p<0.001). From 22 patients treated in our institution, 59% were male with a mean age of 9.7 years, 50% occurred in the posterior fossa and 77% treated by surgery only. One patient relapsed and died from disease (BRAF V600E positive) (follow-up median=44.7 months). These are the first results using a CLIA method showing the frequency of BRAF abnormalities in a Brazilian population. Although preliminary, BRAF alterations are present in 61% of the cases emphasizing the importance of incorporating this analysis in the current work-up guidelines.