Because the expression of Notch1 is not restricted to the ductal epithelial cells and Notch1−/− mice died in utero (24), to evaluate the impact of Notch1 inactivation in tumor-intrinsic and -extrinsic manners, we generated Notch1+/−;p16fl/fl;LSL-KrasG12D;p48-Cre (N1+/−PKC) and Notch1fl/fl;p16fl/fl;LSL-KrasG12D;p48-Cre (N1fl/flPKC; Supplementary Fig. S1A). The gene discussed is NOTCH1; the disease is neoplasm.