fig9

Figure 9. Genetic lineage of BSC. A: activating SHH pathway mutations initially drive formation of BCCs. Acquisition of de novo ARID1A mutations or other chromatin remodeling mutations under pharmacological SMO inhibition drive cellular plasticity, pushing basal cells to undergo squamatization and leading to BSC formation; B: within the BCC zone, high levels of SHH signaling, low RAS/MAPK pathway activity, and high levels of ciliation drive tumor growth. Within the SCC zone, RAS/MAPK signaling increases with a concomitant reduction in SHH pathway activity and ciliation. Within the transition zone, ce3lls begin to show higher levels of RAS/MAPK pathway activity while maintaining SHH signaling. The levels of ciliation are unknown. SHH: sonic hedgehog; BCC: basal cell carcinoma; SMO: Smoothened; BSC: basosquamous cell carcinoma