Fig. 4: Age-associations in nuclear and mitochondrial SNVs reveal ATRX as an age-associated prognostic biomarker in lower grade glioma.

A Summary of age- associated nuclear driver SNVs for (A) pan-cancer and (B) tumour-type specific analyses across three datasets. Dot size shows the magnitude of the association as the difference in proportion and the background shading shows FDR-adjusted multivariate regression (MV) p values. Left covariate in (B) indicates relevant tumour-type. C TCGA lower grade glioma (n = 515 biologically independent samples) age-associations in driver mutation frequency with adjusted multivariate p values, marginal log odds changes for 10-year age increment, and age of tumours compared between those with (red) and without (grey) the mutation. D Summary of age-associated mitochondrial SNVs in PCAWG with specific examples from ovarian cancer data (n = 110 biologically independent samples) shown in (E). F Mitochondrial copy number foldchange is also associated with age in four tumour contexts. G In TCGA lower grade glioma (n = 515 biologically independent samples): mRNA abundance changes for IDH1 and ATRX when the gene is mutated (red) or not (black) compared by median-dichotomised age. Adjusted SNV-age interaction p values are shown. H ATRX mutation interacts with age to stratify lower grade glioma patient prognosis into four groups. Log-odds p value is shown. 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. For (C and E): tumours with indicated mutation shown in red, without in grey, and coefficient estimate from linear modeling and 95% confidence intervals shown. Source data are provided as a Source Data file.