PIK3CA and glioblastoma: In GBM, the RAS-RAF-MAPK pathway is most frequently affected by activating alterations to the membrane receptors, such as EGFR, and more rarely by genetic alterations of downstream effectors such as NF1 and BRAF.37 Interestingly, we found that tumors harboring an NF1 alteration were not associated with co-mutations in the EGFR gene or the PIK3CA gene.