LG-24: BRAF ALTERATIONS IN PEDIATRIC PILOCYTIC ASTROCYTOMAS WITH RECURRENCES/PROGRESSION

Tandem duplication of BRAF and the resultant fusion oncogenes causing constitutive activation of the RAS/MAPK pathway is the most common genetic alteration seen in pediatric pilocytic astrocytoma (PA). The indolent behavior of PAs maybe due to BRAF activation-induced senescence. Our objective was to review molecular alterations and correlate with clinical outcomes in patients with recurrent/progressive PAs. Between the years 1997-2013, 153 patients were diagnosed with PA. Of 31 patients (20.3%) that experienced recurrence/progression, BRAF V600E mutation by immunohistochemistry and BRAF duplication by fluorescent in-situ hybridization were conducted in 18 patients with available tumor tissue (initial diagnosis: n = 10; recurrence/progression: n = 8). Median age at diagnosis was 9.87 years (range; 1.1-19.1 years). Four patients had disseminated disease. Tumor site included deep/midline (61%), cerebellum (28%), and cerebrum (11%). Median follow-up time was 8 years (range; 0.34-11.9 years). BRAF duplication was noted in 61% (n = 11), rearrangements in 11% (n = 2), and polysomy 7 in 11% (n = 2). BRAF V600E mutation was noted in 1 patient. Median time to recurrence was 1.24 years (range; 0.2-3.3 years) and 1 year (range; 0.5-1.8 years) in the BRAF duplication positive and negative groups, respectively. No significant association was noted between age, sex, degree of resection, tumor location, or tissue sample timing (initial diagnosis versus recurrence/progression) and presence of BRAF duplication events. BRAF duplication is the most common genetic alteration even among the subset of patients who have recurrent/progressive PAs. The possibility of additional genomic alterations that allows tumor proliferation by overcoming the BRAF oncogene-induced senescence in PAs requires further study.