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Fig. 1 | Clinical Epigenetics

Fig. 1

From: Extensive intratumor regional epigenetic heterogeneity in clear cell renal cell carcinoma targets kidney enhancers and is associated with poor outcome

Fig. 1

Strategy for defining intratumoral heterogeneity and summary of pathology-level heterogeneity within our ccRCC cohort. A Summary of sample acquisition methodology to profile 5mC in distinct tumor regions. Multiple regions of each resected tumor are fixed in FFPE blocks, sectioned, and embedded on microscopic slides. Sequential slides from each block are divided into sections that are assessed independently for H&E, IHC, and 5mC. In panel A (bottom), we illustrate pathology-level ITH represented as different nuclear grade and H3K36me3 levels between neighboring regions of the same tumor. DNA is extracted from these sections independently for downstream analysis. Figure created with Biorender.com B Oncoprint showing patient-level results (SETD2 mutational status, metastasis, and T stage) of all 12 ccRCCs, and below that region-specific results (nuclear grade, necrosis, SSIGN score, H3K36me3 IHC status, and 5mC IHC status). Tumors are grouped according to their SETD2 mutational status (wt to the left and mt to the right). P-values are the outcome of χ2 comparison of each criterion between SETD2 wt and mt tumors. Some tumor regions could not be scored (NR, white blocks). C Barplots showing a significant pairwise association of 5mC with H3K36me3 (Neg = negative, Pos = positive) and SSIGN score, H3K36me3 with SSIGN score, and nuclear grade with necrosis (P = present, A = absent) and SSIGN score. Frequencies are plotted on the y-axis, and count is indicated in each section of the colored bars

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