Fig. 4: Growth modes impact the spatial features of parallel evolution and youngest subclones.
a, Distance from regions harbouring parallel mutational events that span a single region to the tumour margin. Red rectangles indicate the two representative cases shown in b. b, Maps of regions containing parallel mutation events in two representative cases (PBRM1 events in K520 (i) and BAP1 events in K252 (ii)) in the TRACERx Renal study. Distinct parallel mutation events are indicated using different colours. For regions containing more than two parallel mutations, two colours are applied simultaneously. Double-headed arrow indicates the measurement of distance to tumour edge. c, Schematic of the analysis of youngest subclones within a 2D tumour slice. d, Distance from the positions of youngest subclones to the tumour margin, in models without (i) or with (ii) the implementation of necrosis. n = 100 youngest subclones from each simulation are analysed and shown as grey points, with the mean distance to margin indicated with a coloured vertical bar. n = 50 simulations are shown, arranged from small to large mean distance to margin (top to bottom) for each model condition. Surface growth and volume growth models are shown in red and blue, respectively, with increasing driver acquisition probabilities indicated by increasing colour intensity. e, Distance from regions harbouring genomic alterations that span a single region to the tumour margin. Only tumours with at least ten regions are included. Red rectangles indicate the two representative cases shown in f. f, Maps of regional biopsies with the number of subclones within a biopsy colour coded in two representative cases (K523 and K156) in the TRACERx Renal study. Hues from red to purple to blue reflect decreasing number of subclones. ‘Low’ and ‘High’ reflect one and four subclones in K523 or one and six subclones in K156, respectively. Regions harbouring events that span a single region are marked by arrows, green if located within 10 mm from the tumour edge and orange otherwise. g,h, Histological images of representative areas from tumour regions of K156 (g) and K523 (h). Vertical dashed line in a,d and e corresponds to a distance of 10 mm.
