Fig. 4. Interferon signaling suppression drives expansion of aneuploid RCC clones.
a, Circos plots of the human to mouse synteny map for chromosome regions significantly lost in SM-GEMM tumor-bearing mice, generated by the SynCircos function of Synteny Portal. Magnification of the human chromosome 21 region shows the genomic location and coordinates of the IFNR cluster. b, Violin plot displaying interferon (Ifn) score calculated for four different groups clustered by genomic data (P < 1 × 10−15, n = 87,718 cells). c, Violin plots displaying expression values of Isg15 (top) and Irf7 (bottom) calculated for four different groups clustered by genomic data (P < 1 × 10−15, n = 87,718 cells). d, Three-dimensional distribution of the Ifn score values for all the cells. e, Three-dimensional representation of two subpopulations with high values of Ifn score (left panel) and low values of Ifn score (right panel), displaying the distribution in the four different genomic groups and pseudotime values. n = 87,718 cells. f, Expression values of two genes involved in chromosome stability and mitotic checkpoint in the Ifn low and Ifn high groups; P < 1 × 10−15. n = 37,624 cells. g, Violin plot displaying the CNV score in the ‘Ifn high’ and ‘Ifn low’ groups; P < 1 × 10−15. n = 37,624 cells. h, Violin plot displaying fCNA values across different tumors with 9p− or 9p− and 21q−, with or without WGD, in two different cohorts: TCGA-KIPAN (left panel), P = 2.76 × 10−7, 1.67 × 10−2 and 1.46 × 10−5; MSKCC (right panel), P = 1.76 × 10−4 and 5.77 × 10−5. n = 922 tumors. i, Volcano plot showing top upregulated and downregulated pathways, comparing 9p− and 21q− tumors versus 9p− tumors in the TCGA-KIPAN transcriptomic dataset. n = 788 tumors. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001 by two-tailed Mann–Whitney test (b,f–h). Rej., rejection; resp., response; TGCA-KIPAN, TCGA pan-kidney.