Given that deregulation of the interplay between ASCL1 and NDRG1 might be considered as an initiating molecular event involved in the progression from PN to MES subtypes, a better understanding of the mechanisms underlying gene expression changes (e.g., microenvironment-induced gene repression and derepression, etc.)may lay the foundation for the identification of therapeutic strategies specifically targeted to restrain PMT and GBM evolution. The gene discussed is ASCL1; the disease is Meckel syndrome, type 1.