While the biallelic loss of NF1 is a well-established activating event in syndromic NF1 and its associated malignancies like glioma, leukemia, plexiform neurofibroma, MPNST, and melanoma16–18, the impact of ALK amplification, low EGFR copy number gain, and SUZ12 biallelic deletion on both MAPK pathway activation and sensitivity to MEK inhibitors is less certain. This evidence concerns the gene ALK and central nervous system cancer.