Abstract
Pilocytic astrocytoma (PA) is a benign grade 1 glioma according to the World Health Organization (WHO). It is frequent in pediatric population, but very rare in adults, where it can be associated with worse prognosis. Molecular features of pediatric PA are associated with dysregulation of the MAPK pathway, most often showing BRAF alterations such as the KIAA1549::BRAF (K-B) fusion or the V600E mutation. Here we analyze the molecular characteristics of adult PA through gene-targeted next-generation sequencing (NGS) and single gene tests (K-B fusion, and TERT promoter and FGFR1 hotspot mutations). In adults, the most frequent molecular alterations detected involved the MAPK pathway, namely affecting with BRAF and NF1 genes (16/29, 55%). Our study reveals that the prevalence of the K-B fusion (44.5%), is higher than what was reported in other adult PA series, probably due to technical difficulties in detecting the fusion. This molecular alteration was not associated with recurrence, but worse outcome was observed in patients with additional alterations, in particular oncogenic ATRX mutations. Furthermore, our results unveiled a subset of cases showing molecular alterations that raise differential diagnosis with other tumor types, thus demonstrating limitations of the current 2021 WHO classification in adult PA. In summary, our study suggests that PA in adults is a single-hit disease, as is the case in the pediatric population.