Figures S1-S10 from Sarcomatoid Renal Cell Carcinoma Has a Distinct Molecular Pathogenesis, Driver Mutation Profile, and Transcriptional Landscape
Figure S1. Biphasic histologic components of sarcomatoid renal cell carcinoma. The macrodissected paired epithelioid or carcinomatous (E) and spindled or sarcomatoid (S) components of clear cell RCC (upper panel), Papillary RCC (middle panel), and chromophobe RCC (lower panel). H&E stain, scale bar 200 ï�m. Figure S2. Sarcomatoid ccRCC shows fewer VHL deletions. (A) Clear cell RCC (H&E stain, scale bar 100 µm) with (B) Fluorescence in situ hybridization (FISH) image showing paired CEN3q signals (green) and a single VHL signal (red). (C) Sarcomatoid ccRCC (H&E stain, scale bar 100 µm) with (D) FISH image showing balanced CEN3q (green) and VHL (red) signals. (E) Box plot showing significantly higher VHL/3q ratios associated with sarcomatoid histology, P<0.008. Figure S3: The smooth scatter plot of signal B versus signal A. Figure S4a: 3p21 and 3p21.1 copy number versus chromosome position. Figure S4b: 3p25 copy number versus chromosome position. Figure S5: Kernel density plots. Each sample per row; left three columns: 3p21; middle three columns: 2q37; and right three columns: 1p1. Figure S6a: Example of more than one peak in the summed signal. Figure S6b: Example of 4 peaks in signals A and B. Figure S7: Density plots of TCGA samples with copy-neutral LOH. Figure S8. VHL and PBRM1 show fewer 2-hit inactivation in sarcomatoid ccRCC. Sarcomatoid ccRCC and ccRCC cases shown in terms of the inactivating "hits" on 3p21-25 genes (VHL, PBRM1, SETD2, BAP1) consisting of mutations or methylation (mutually exclusive for VHL) and deletions. Figure S9. Top activated and inhibited pathways of sarcomatoid samples. Pathways altered by differentially expressed genes between non-sarcomatoid and sarcomatoid samples. The genes selected were differentially expressed in both the TCGA and MD Anderson samples. Figure S10. S- component shows a higher mutational load in sarcomatoid RCC. The total number of non-synonymous mutations in the E- and S- components of sarcomatoid RCC, across all parent RCC subtypes (A) and in clear cell RCC (B).
