BRAF G469A, BRAF L597V, FGFR1 N546K, FGFR1 K656E and P53 R273H mutations: How are they distributed in Moroccan patients with pediatric Low-Grade Gliomas?

Abstract

BackgroundLow-Grade Gliomas are common brain tumors in children. They are known for their heterogeneity, especially their molecular heterogeneity. This makes their definition and classification based only on histological criteria difficult and lacking in precision. If this presented a limit to progress in the understanding of these tumors, advances in molecular biology and molecular genetics have allowed us to deepen our knowledge of the nature of these tumors and the way they develop, which helps us considerably in improving their classification, diagnosis and treatment. AimWe identified the distribution of BRAF G469A, BRAF L597V, FGFR1 N546K, FGFR1 K656E and P53 R273H mutations in Moroccan patients with pLGGs, according to their sex, age, brain tumor location and subtype and we compared the results with their distribution in Moroccan patients with pHGGs. MethodologyWe studied BRAF G469A, BRAF L597V, FGFR1 N546K, FGFR1 K656E and P53 R273H mutations in 89 pLGG tissues by comparing them with 123 hLGG tissues, using PCR-RFLP and TaqMan. Data was analyzed by using IBM SPSS software v24. ResultsBy studying the involvement of the BRAF G469A mutation, the BRAF L597V mutation, the FGFR1 N546K mutation, the FGFR1 K656E mutation and the P53 R273H mutation in the development of Pediatric Low-Grade Gliomas, we obtained significant results for the BRAF L597V mutation. 6.7% of the pLGG patients studied were carriers of this mutation (P = 0.0450). (2/2) of these patients with the tumor localized in the hemispheres, (1/8) in the SAI nervous system and (3/29) in the spinal cord were positive. As for the P53 R273H mutation, (19/78) of the pLGG positive cases were Pilocytic Astrocytomas, (1/4) Pilomyxoid Astrocytomas and (4/6) Diffuse Gliomas. By studying the different interactions between the mutations, we obtained significant interactions between the presence of the BRAF L597V mutation and the absence of the BRAF G469A mutation (P = 0.0415), the presence of the BRAF L597V mutation and the absence of the FGFR1 N546K mutation (P = 0.0448) and the presence of the FGFR1 K656E and P53 R273H mutations (P = 0.0056). ConclusionIn our future studies, we plan to continue in the same vein and explore other mutations suspected to be involved in the development of pediatric Low-Grade Gliomas. Studying them would be an opportunity to understand the origin of these tumors but also a field to improve their classification and thus their diagnosis and treatment.