Mutations of BRAF in low-grade Astrocytomas

Abstract

Pilocytic astrocytomas (PA) are the most common brain tumors of childhood. Neurofibromatosis type I (NF1) is an autosomal dominantly inherited disorder associated with PA. Patients with a mutation of the NF1 gene have a dysfunction of neurofibromin. Neurofibromin normally leads to a down-regulation of the Ras signaling pathway due to a GAP domain (GTPase-activating protein-related domain). In patients with NF1 an increased activity of Ras can be measured. Further genetic diseases such as Noonan syndrome, LEOPARD syndrome, Cardio-Facio-Cutaneous syndrome, and Costello syndrome also go along with an activation of the Ras pathway. Somatic mutations in the genes responsible for these syndromes (PTPN11, KRAS, BRAF, HRAS) are involved in the formation of malignant tumors. In few sporadic PA mutations of KRAS have been detected.