Extended Data Fig. 3: KMT2C deficiency in SCLC metastases and its function in lung organoids.
(a) The Venn plot showing the mutation frequency of epigenetic regulatory genes in Module I. (b) The Ridge plot showing gene ontology enrichment in the Ascl1 + primary SCLC cells, analyzed by GSEA. (c) The Kaplan-Meier survival curves of SCLC patients with low and high expressions of KMT2C. Calculated by log-rank test. (n = 42, low; n = 35, high) (d) Representative western blotting pictures of H3K4me1 and H3K4me2 in the PRM and PRM-Met SCLC cells. Three independent repeats. (e) Representative staining of KMT2C, H3K4me1and H3K4me2 of the PRM primary (n = 3) (left) and PRM-Met (n = 3) liver sections (right). Scale bar, 40 µm. (f) The levels of H3K4me1 bound at the enhancers in the PRM and PRM-Met tumor cells, measured by the CUT&Tag analyses. (g) Genome-wide distribution of the H3K4me1 up-regulated genes (top) and down-regulated genes (bottom) in PRM-Met compared to PRM, measured by CUT&Tag analyses. (h) T7 endonuclease 1 (T7E1) assays showing the mutations of Kmt2c in the premalignant PRM organoids. Three independent repeats. Cleaved bands were pointed by arrowheads. (i) Dynamics of relative expression levels of Cyp2f2, Notch1 and Mki67 on the normal development (black line) and malignant transformation (purple line) trajectories.
