Fig. 3. The drivers of clonal hematopoiesis.

a Logistic regression showing the relationship between several factors and the development of CH across 3121 donors with treatment annotation in the metastasis cohorts. For this analysis, a donor is considered to suffer CH if they bear a nonsilent mutation in a CH gene discovered in the analysis of the primary and/or metastasis cohorts. The age of the donors in these cohorts as well as their prior exposure to cytotoxic therapies significantly increase their likelihood of presenting clonal hematopoiesis. The bars represent the 95% confidence interval of the regression coefficients. P-values correspond to the results of the logistic regression. b Logistic regression showing the relationship between the presence of mutations in several genes and the prior exposure of donors in the metastasis cohort to platinum-based therapies across 3121 donors with treatment annotation in the metastasis cohort. Mutations in CHEK2 and PPM1D are significantly more likely detected across platinum-exposed donors. The bars represent the 95% confidence interval of the regression coefficients. P-values correspond to the results of the logistic regression corrected by multiple tests carried out separately for different treatments. c Distribution of blood somatic mutations affecting seven genes selected from the CH drivers compendium across donors of the primary and metastasis cohorts (above the horizontal axis) in comparison to those observed in the same genes across 28076 tumors analyzed by the IntOGen resource²⁵ (below the horizontal axis). d Relationship between the fraction of truncating variants identified in genes with 10 or more mutations across blood samples in the primary and metastasis cohorts and across several cohorts of tumors²⁵. The mutations in tumor samples have been obtained from the IntOGen resource. The p-value corresponds to the Pearson’s correlation coefficient. Source data for panels a, b, c, and d are provided as Source Data files.