MYC-driven SCLC can arise in multiple lung cell types and initially expresses ASCL1. (A) Survival of RPM mice infected with indicated cell type-specific Ad-Cre viruses. Number of mice indicated in the figure. Mantel-Cox log-rank test, (****) P < 0.0001. (B) Representative H&E histology of SCLC from RPM mice initiated with indicated Ad-Cre viruses. Scale bar, 25 µm. (C) Representative immunohistochemistry (IHC) of early in situ tumor lesions for indicated neuroendocrine (NE) or non-NE markers (top) in RPM mice infected with indicated Ad-Cre viruses (left). Arrows indicate in situ tumors. Images shown are from mice collected at approximately the following time points postinfection: CMV 43 d, CGRP 55 d, CCSP 80 d, and SPC 180 d. Scale bar, 25 µm. (D) Representative IHC of large, invasive tumors for indicated neuroendocrine (NE) or non-NE markers (top) in RPM mice infected with indicated Ad-Cre viruses (left). Images shown are from mice collected at approximately the following time points postinfection: CMV 43 d, CGRP 55 d, CCSP 80 d, and SPC 180 d. Scale bar, 25 µm. (E) H-score quantification of IHC in C and D. H-score = percentage positive cells multiplied by intensity score of 0–3 (see the Materials and Methods). Approximately 70–200 tumors from three to 10 mice per condition were quantified. Data are shown as mean ± standard deviation (SD). Mann-Whitney two-tailed t-tests, (**) P < 0.01, (****) P < 0.0001. See also Supplemental Figure S1.