LG-68: THE GENETIC AND CLINICAL LANDSCAPE IN PEDIATRIC LOW GRADE GLIOMA; PRELIMINARY RESULTS FROM PLGG TASKFORCE

BACKGROUND: Alterations of the RAS/MAPK pathway have been identified as the major driver of pediatric low-grade gliomas (PLGG) however the prevalence of specific lesions and prognostic implications are unknown. METHODS: We undertook a population based study of all PLGG diagnosed from 2000-2015. Analysis included QX200™Droplet Digital™PCR, NanoString and copy number profiling. Findings were correlated with pathology, demographics and outcome. RESULTS: Sufficient tissue for BRAF-V600E, BRAF-fusions, FGFR1-TACC1 and MYBL1 was available on 310 out of 450 biopsied patients. In decreasing frequency were BRAF-KIAA1549 fusion (38%), BRAF-V600E (14%), FGFR1-TACC1 (3%) and MYB1 alteration (1%). 44% PLGG had none of these alterations. The percent represented by each alteration varied depending on pathology and tumor location. In addition to the high prevalence of BRAF-KIAA1549 in pilocytic astrocytoma, it was found also in ganglioglioma (13%) and diffuse astrocytoma (10%). In low-grade astrocytoma, NOS BRAF-V600E and BRAF-KIAA1549 were evenly distributed, each found in 20% of cases, while in pleomorphic xanthoastrocytoma and ganglioglioma BRAF-V600E was most frequent. BRAF-KIAA1549 was found in only 10% of non-midline gliomas, MYBL1 is most prevalent in diffuse astrocytomas and exclusive to the hemispheres, while BRAF-V600E prevalence was similar in hemispheres, diencephalon and brainstem (20-30%). BRAF-V600E PLGG has significantly worse PFS when compared to NF-1 or BRAF-fused. All patients with FGFR1-TACC1 and MYBL1 are still alive. CONCLUSIONS: Our study constitutes the largest PLGG cohort assembled to our knowledge and provides a robust characterization of the clinical and genomic landscape of PLGG. This has tremendous implications in the planning and accessibility of targeted therapies.