LGG-60. THE GENETIC LANDSCAPE OF PEDIATRIC LOW-GRADE GLIOMAS: INCIDENCE, PROGNOSIS AND RESPONSE TO THERAPY. Issue 2 (22nd June 2018)

• Record Type: Journal Article
• Authors: Ryall, Scott; Zapotocky, Michal; Fukuoka, Kohei; Guerreiro-Stucklin, Ana; Bennet, Julie; Arnoldo, Anthony; Kowalski, Paul; Johnson, Monique; Lassaletta, Alvaro; Bartels, Ute; Huang, Annie; Ramaswamy, Vijay; Ellison, David; Tabori, Uri; Hawkins, Cynthia
• Is Part Of: Neuro-oncology. Volume 20:Issue 2(2018)supplement 2
• Page Start: i117
• Page End: i117
• Publication Date: 2018-06-22
• Subjects: Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noy059.400
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: Molecularly characterization of pediatric low-grade glioma (pLGG) over the last decade has identified recurrent alterations, most commonly involving BRAF, and less frequently other pathways including MYB and MYBL1. Many of these molecular markers have been exploited clinically to aid in diagnosis and treatment decisions. However, their frequency and their prognostic significance remain unknown. Further, a significant portion of cases do not have any of these alterations and what underlies these cases is also unknown. To address this we compiled a cohort of 562 patients diagnosed at SickKids from 1990-2017. We identified molecular alterations in 454 (81%) of the cohort. The most frequent events were those involving BRAF; either as fusions (most commonly with KIAA1549 (30%)), or V600E mutations (17%) and NF-1 (22%). Less frequently, we identified recurrent FGFR1 fusions and mutations (3%), MYB/MYBL alterations (2%), H3F3A_K27M mutations (2%) and IDH1_R132H (0.5%), as well as other novel rare events. Survival analysis revealed significantly better progression-free survival (PFS) and overall survival (OS) of BRAF-KIAA1549 patients compared to BRAF_V600E with 10-year OS 97.7% (95%CI 95.5-100) and 83.9% (95%CI 72.5-95.6) respectively. In addition to survival, the molecular alterations predict differences in response to conventional therapeutics; BRAF fused patients show a 46% response-rate, versus only 14% in V600E patients. pLGG harboring H3F3A_K27M progressed early with median PFS of 11 months. In patients with MYB/MYBL1, FGFR1/FGFR2 alterations, we observed only one death (FGFR1_N546K case). The work here represents the largest cohort of pLGGs with molecular profiling and their impact on the clinical behaviour of the disease.