Analysis of genetic aberrations in pediatric low-grade gliomas: the experience of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology

Abstract

Low grade gliomas (LGGs) are the most common brain tumors in children. Our retrospective-prospective study of biological characteristics of sporadic LGGs (not associated with neurofibromatosis type I) included 233 patients aged 0 to 18 years who had been diagnosed and/or treated at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology in the period from 2009 to 2021. The study was approved by the Independent Ethics Committee and the Scientific Council of the D. Rogachev NMRCPHOI. The median age at the diagnosis was 5 years 4 months (2 months – 17 years). Among the LGGs, the following histological variants were identified: pilocytic astrocytoma (n = 191; 82%), pleomorphic xanthoastrocytoma (n = 16; 7%), ganglioglioma (n = 7; 3%), desmoplastic infantile ganglioglioma (n = 4; 2%), diffuse leptomeningeal glioneuronal tumor (n = 5; 2%), dysembryoplastic neuroepithelial tumor (n = 2, 1%), and diffuse astrocytoma (n = 1; 0,5%). The tumors were located in: the suprasellar region (n = 98; 42%), the brainstem (n = 40; 17%), the cerebellum (n = 35; 15%), the hemispheres (n = 34; 15%) etc. The KIAA1549-BRAF fusion was the most common molecular genetic alteration (n = 107; 46%). The second most frequent genetic aberration was the BRAF V600E mutation (n = 44; 19%). Rare molecular genetic events leading to the activation of the MAPK signaling pathway were detected in 13 (6%) patients. The H3 K27M mutation associated with an aggressive clinical course was identified in three patients with brainstem LGGs (1%). These findings point to the importance of molecular profiling of pediatric LGGs for the selection of an effective strategy for molecular diagnosis and optimal clinical care.