Fig. 7

Rbl2 co-mutations accelerate SCLC tumorigenesis. a Sequential MRI of a representative AV-PR.Cre and AV-PRL.Cre infected mouse illustrating different kinetics of tumorigenesis. Shown are frontal and transversal sections with tumors marked in color. b Histological analysis of AV-PR.Cre and AV-PRL.Cre induced lung tumors. Shown are representative H&E and immunohistochemical stains for Cas9, GLuc and NE lineage markers (Ascl1, Synaptophysin, Chromogranin). c Quantitative analysis of SCLC tumor burden, tumor number and tumor size in AV-PR.Cre (n = 12) and AV-PRL.Cre (n = 17) infected mice. Shown is mean ± SD and P-values from unpaired, two-sided t-tests. d Trp53, Rb1 and Rbl2 mutation spectra of single tumors from 5 different mice of each group. Top graph, shown is the frequency of wild-type and mutant reads. For mutant reads, all mutations with a frequency of > 5% are color-coded as deletions or insertions and labelled with the number of deleted, inserted or substituted base pairs. Less frequent mutations are summarized as ‘others’. Bottom graph, shown is the size distribution of indel mutations for each tumor. The frequency of each indel mutations is encoded in grayscale