Fig. 2: Age-associated mutational signatures suggest differences in underlying mutational processes.
From: Age influences on the molecular presentation of tumours
A In TCGA lung adenocarcinoma adenocarcinoma (LUAD; n = 497 biologically independent samples), age (top plots) and PGA (bottom plots) are associated with the tobacco-associated signature SBS4 (left; two-sided Wilcoxon rank sum test). Yellow and blue dots indicate SBS4− and SBS4+ tumours, respectively. The absolute number of SBS4-attributed mutations is also associated with age and PGA (middle; Spearman correlation). The relative proportion of SBS4-attibuted mutations is negatively associated with age and has no significant relationship with PGA (right; Spearman correlation). B The negative association between PGA and age in LUAD remains significant in both SBS4+ (blue) and SBS4− (yellow) groups (Spearman correlation). C Summary of associations between age and the proportion of signature-positive tumours, where dot size shows the marginal log odds from logistic regression and background shading show adjusted multivariate p values. PCAWG data is on left and TCGA on right. D Similarly, the summary of associations between age and relative signature activity, with dot size showing Spearman correlations and background indicating adjusted linear regression p values. E Comparison of PCAWG and TCGA signature detection frequency. Filled in and open circles indicate comparisons where the differences are statistically significant (proportion test FDR-adjusted p < 0.05) and not, respectively. Proposed SBS signature aetiologies are as indicated. Proposed DBS and ID aetiologies are: DBS1: UV, DBS2: tobacco, DBS5: platinum chemotherapy, DBS7: defective MMR, ID1: slippage during DNA replication, ID2: slippage during DNA replication, ID3: tobacco, ID6: defective homologous recombination, ID8: non-homologous end joining, ID13: ultraviolet radiation. Tukey boxplots are shown with the box indicating quartiles and the whiskers drawn at the lowest and highest points within 1.5 interquartile range of the lower and upper quartiles, respectively. Source data are provided as a Source Data file.
