Fig. 4: Tumor evolution.
a, Comparative molecular profiling of pathogenic mutations and CNVs in paired plasma baseline and relapse samples from 12 participants with CC. Each box signifies a mutated gene in an individual participant, with division into two parts separated by a line. Left, results obtained at baseline. Right, results from plasma at relapse. Similarly, each box corresponding to a collection moment is subdivided into two components. Left, point mutations. Right, CNVs. The y axis is organized on the basis of the number of point mutations for each gene across all participants. b, Evolutionary plot in the discovery cohort for seven paired participants (top) and the validation cohort for 14 paired participants (bottom), illustrating somatic mutations occurring at baseline, after surgery and at relapse. Colors indicate the presence of mutations over time, with gray representing mutations appearing at baseline but representing unselected subclones lost after surgery. The indications of the sampling time points are not drawn to time scale. Moving along the chromatic scale from green to purple signifies mutations persisting over time and considered clonal. Mutations emerging after surgery until relapse are represented in shades of red, indicating clones arising during tumor evolution in this period. Right, upset plot indicating the correspondence of colors with temporal points where the mutation was found. c, Spearman correlation (n = 7 participants; two-sided) between the B cell infiltration and mutational concordance between baseline and relapse plasma in the discovery cohort. Left, correlation between infiltrated B lymphocytes using RNA-seq deconvolution through the CIBERSORT pipeline versus the mutational concordance. Right, correlation of the intensity of CD20 positivity by IHC in the primary tissues versus mutational concordance. Representative images of some of the participants from CD20 IHC on the primary tissues are indicated. Colors are included for each of the different participants (points) to allow comparison to the validation data using IHC with CD20. The line represents the fitted relationship between the variables, while the shaded band corresponds to the 95% confidence interval around the regression estimate. d, Functional enrichment analysis by hallmark gene sets revealed enriched pathways in mutated genes in the discovery cohort (top; n = 7 participants) and the validation cohort (bottom; n = 14 participants). A one-sided hypergeometric test was used to assess whether the input gene set was significantly overrepresented in hallmark gene sets compared to a background set of genes. The P values were adjusted for multiple comparisons using the FDR correction, with a significance threshold of 0.05.
