Resistance mechanism involving SMO mutation are known in BCC, were described in medulloblastoma preclinical studies and only once in an extra-neural SHH medulloblastoma.16,33,41,42 However, a SMO p.G416D mutation—the same as patient #4—was described, concomitant with a PTCH1 loss of function, in a different case of an adult with SHH medulloblastoma without any previous SMOi exposure.32 One hypothesis to explain why that these 2 mutations can coexist, is that SMO activating mutation is an early subclonal event in PTCH1 mutated medulloblastoma, and that SMOi treatment selects a resistant clone. The gene discussed is PTCH1; the disease is skin basal cell carcinoma.