Fig. 4: The subclonal hallmarks of tumour hypoxia.

We associated tumour hypoxia with features related to the subclonal architecture of 1188 independent tumours from 27 cancer types using linear mixed-effect models. a Hypoxia scores are shown along the top while Bonferroni-adjusted p-values are shown on the right. Hypoxia was not associated with the number of subclones in the tumour but elevated hypoxia was associated with a higher number of clonal mutations. b We also observed a significant interaction between hypoxia and altered PTEN where tumours with both of these features were particularly likely to be polyclonal. c The mRNA abundance of PTEN is modulated by both PTEN mutational status and tumour hypoxia. Tumours with altered PTEN and elevated hypoxia have the lowest abundance of PTEN mRNA. mRNA abundance is reported as FPKM with upper-quartile normalization. A Tukey box plot is shown. Box plots represent the median (centre line) and upper and lower quartiles (box limits), and whiskers extend to the minimum and maximum values within 1.5× the interquartile range. All associations were modelled using linear mixed-effect models while adjusting for cancer type, tumour purity, age and sex. d Altered PTEN and hypoxia may drive subclonal diversification. Many primary tumours have elevated hypoxia due to increased demand or decreased supply of oxygen. Tumours with elevated hypoxia tend to have altered PTEN. Elevated hypoxia and altered PTEN may drive subclonal diversification and poor outcomes.