PATH-14. MOLECULAR ANALYSIS OF ASTROCYTOMAS WITH A DOMINANT PILOMYXOID MORPHOLOGY

Abstract

Abstract Pilomyxoid astrocytomas (PMAs) are tumors of infancy occurring in the hypothalamic chiasmatic region, with somewhat worse prognosis than pilocytic astrocytomas (PAs). We report molecular findings in PAs with a dominant pilomyxoid histomorphology across the various age groups and CNS locations. Foundation Medicine comprehensive genomic profiling (CGP) (FoundationOne, FoundationOneCDx, FoundationOneHeme) were performed during routine clinical care. A retrospective cohort analysis was done to evaluate the genomic characteristics of PMAs. 57 PMAs were identified, of which 6 occurred in patients < 12 months old (10.5%); 14 in 1-3 year old (24.6%); 15 in 4-10 y.o. (26.3%); 12 in 11-20 y.o. (21.1%), and 10 occurred in young adults 21-39 y.o. (17.5%). 30/57 (52.6%) were female and 27/57 (47.4%) male. 55 PMAs occurred in the brain and 2 in the spinal cord. Tumors were categorized by notable rearrangements and point mutations. The common fusion, KIAA1549:BRAF, was detected in 23/57 samples (40.4%). BRAF fusions with other gene partners (BRAF, TAX1BP1) occurred in 2, and BRAF V600E mutations in 4 patients. An additional 4 patients had FGFR1 fusions (FGFR1, TACC1) and 14 had FGFR mutations. Other alterations included 3 NF1 mutations, 2 NTRK family receptor tyrosine kinase fusions, 2 RAF gene fusions, 2 other (ATRX, ALK) alterations, and 1 VUS. Tumor Mutational Burden was under 10 mut/Mb for all patients. In this cohort of 57 PMAs, MAPK pathway genetic alterations were dominant drivers, similar to other PAs. We also observed other frequent genetic alterations not involving BRAF, including FGFR and NTRK gene family members that have FDA approved targeted inhibitors. While these also likely cause MAPK pathway activation, these non-BRAF variants are less common in PAs. Our report contributes to growing evidence that PMAs harbor a distinct molecular alteration profile, which is becoming increasingly important in the context of the evolving targeted therapeutics landscape.