LGG-36. Analysis of BRAF-related mutations in pediatric low-grade glioma

Abstract

BACKGROUND: Most pediatric low-grade gliomas (pLGGs) are driven by a single genetic event resulting in up-regulation of the RAS/MAPK pathway. BRAF-related mutations are the most freauent molecular alteration in the pathway. To explore BRAF-related mutations in pediatric low-grade glioma is helpful for clinical practice. METHODS: In this study, patients with low-grade glioma aged ≤18 years in Guangdong Sanjiu Brain Hospital were enrolled. All patients accepted the tests of BRAF-related mutations with tumor tissue by next-generation sequencing (NGS). Results: A total of 26 patients diagnosed low-grade glioma and underwent NGS detection were included in this study. The male to female ratio was 6:7, and the median age was 9.5 years. 8 patients had tumors located in the cerebral hemisphere, 6 in the third or fourth ventricle, 5 in the cerebellum, 4 in the optic pathway, and 3 in the brain stem. A total of 14 patients took BRAF-related mutations, such as BRAF-KIAA1549 fusion, BRAF p.V600E mutation and other fusion. BRAF-KIAA1549 fusion was detected in 7 patients with pilocytic astrocytoma or pilomyxoid astrocytoma. BRAF p.V600E mutation was detected in 6 patients, two of whom were pleomorphic xanthoastrocytoma. A rare genetic fusion, BCAS1-BRAF fusion, was detected in 1 patient who had brain stem ganglioglioma. Among the 26 patients, 2 patients without BRAF-related mutations had typical multiple cafe-au-lait macules and were diagnosed as NF1-pLGG. These patients were treated with surgery, radiation, chemotherapy and targeted therapy. Only 2 patients received targeted therapy by Trametinib, Vimofinib and Everolimus after progression of the tumor. However, due to the severity of the disease, they eventually died. CONCLUSIONS: More than half of pLGG patients have BRAF-related mutations, which have the opportunity for targeted therapy. However, the optimal timing of targeted therapy still needs further exploration.