NF1 variants

Somatic alterations in NF1 are seen most frequently in children with NF1 and are associated with germline alterations in the tumor suppressor NF1. Loss of heterozygosity for NF1 represents the most common somatic alteration in these patients followed by inactivating variants in the second NF1 allele, and consistent with a second hit required for tumorigenesis. While most NF1 patients with low-grade gliomas have an excellent long-term prognosis, secondary transformation into high-grade glioma may occur in a small subset. Genomically, transformation is associated with the acquisition of additional oncogenic drivers, such as loss of function alterations in CDKN2A, CDKN2B and/or ATRX. Primary high-grade gliomas may also occur in patients with NF1 but are exceedingly rare. Genomic alterations involving the MAPK signaling pathway other than NF1 are very uncommon in gliomas occurring in children with NF1.[8]