Fig. 5: Spatial mapping of ecDNA-driven MYC amplifications and epithelial cell states.
From: MYC ecDNA promotes intratumour heterogeneity and plasticity in PDAC
a, Post-Xenium haematoxylin and eosin of VR06-P (top). The magnifications of ROI-1 (caret; bottom right) and ROI-3 (asterisk; bottom left) demonstrate the different morphology of the neoplastic epithelium. Scale bars, 100 µm. b, Interphase FISH of ROI-1 and ROI-3 from VR06-P (left). Scale bars, 20 µm. Distribution of MYC copy number (CN) states per nucleus with indication of the average MYC copy number per ROI (middle). The dashed red line indicates the median copy number state. In the two selected ROIs, the proportion of nuclei (ROI-1 n = 99 and ROI-3 n = 99) with MYC amplification (defined as copy number > 5) is shown (right). The P value was calculated using Fisher’s exact two-sided test. c, Interphase FISH of ROI-1 and ROI-2 from VR01-P (left). Scale bars, 20 µm. Distribution of MYC copy number states per nucleus with indication of the average MYC copy number per ROI (middle). The dashed red line indicates the median copy number state. In the two selected ROIs, the proportion of nuclei (ROI-1 n = 92 and ROI-2 n = 87) with MYC amplification (defined as copy number > 5) is also shown (right). The P value was calculated using Fisher’s exact two-sided test. d,e, Xenium spatial plots showing localization of LGR5 in the epithelial cells of the selected ROIs (left), and the frequency of epithelial cells expressing LGR5 (middle) and cancer-associated fibroblasts (CAFs) expressing canonical WNT ligands (right) in the selected ROIs from VR06 (d) and VR01 (e). The P values were determined by a Chi-squared test (two-sided). Scale bars, 200 µm. f, Xenium spatial plot showing localization of neoplastic cells classified as either classical or basal-like (left). Scale bars, 200 µm. Distribution of individual epithelial subtypes within the indicated ROIs for each tissue (right). Areas presenting MYC amplification or not are annotated on top.
