Extended Data Fig. 3: Comparison of MYC and RAS in mouse and human prostate cancer.

a–c, Copy number variant (CNV) analyses of KRAS and MYC in mouse and human prostate cancer. a, Kras, Cdkn2a/b and Myc loci, inferred from whole-exome sequencing of NPK^EYFP prostate tumors. Color coding reflects amplifications or deletions in five individual mice (Supplementary Table 4b). b, c, Summary of gains in MYC (b) and KRAS (c) in human prostate cancer comparing primary tumors from TCGA (n = 489) and metastases from SU2C (n = 429) using cBioportal⁴⁹. P values were calculated using a Fisher’s exact test comparing samples with all gains versus no gains. d, e, Box plots depicting Myc pathway and Ras pathway activation in primary tumors and metastases from intact or castrated NPK^EYFP mice (primary tumors: n = 13 intact and n = 6 castrated; lung metastases: n = 9 intact and n = 2 castrated; bone metastases: n = 10 intact and n = 2 castrated). The distribution of the activity scores (y-axis) for Myc activity is based on single-sample GSEA in panel d, and Ras activity levels is based on the absolute-valued average of RAS-related genes as in^11,33 in panel e. P-values were estimated using two-sample one-tailed Welch t-test, boxes show the 25th–75th percentile with the median, and whiskers show the minimum–maximum values. f, g, Violin plots depicting the distribution of MYC and RAS pathway activation in primary tumors and metastases comparing human primary tumors (TCGA, n = 497) versus metastases (SU2C, n = 270). In panel f, the distribution of the NESs (y-axis) represent MYC activity levels based on single-sample GSEA (see Extended data Fig. 4d) In panel g, the activity scores (y-axis) represent RAS pathway activity levels based on the absolute-valued average of RAS-related genes (as in^11,33). P-values were estimated using two-sample one-tailed Welch t-test. In the violin plots with embedded box plots, boxes show the 25th–75th percentile, center-lines show the median, and whiskers show the minimum–maximum values. h, i, Heatmap representation showing the correlation of MYC and RAS pathway activity in mouse (h) and human (i) prostate cancer. Panel h shows Myc and Ras pathway activity in mouse NPK^EYFP primary tumors and bone metastases. Panel i shows MYC and RAS pathway activity in human primary tumors (TCGA, n = 497) and metastases (SU2C, n = 270). Gleason scores are shown for the primary tumors; metastases include all metastases in the SU2C cohort. In panels h, i, Spearman correlation rho- and p-values are shown. j, Mouse NPK^EYFP primary tumors and bone metastases classified as MYC- or RAS-activated are depicted in a heatmap in red, whereas those without MYC- or RAS-activation are represented in blue. Samples were considered Myc-activated if Myc activity scores were greater than the average across the cohorts. Samples were considered Ras-activated if Ras activity scores were greater than the average across the cohorts. The percentage of cases in which Myc and Ras are co-activated are shown; two-tailed p-value was calculated using Fisher’s exact test.