Fig. 5: The role of HLA disruption in tumor evolution.

a, The heterogeneity of HLA LOH, repression and tumor-enriched alternative splicing events. b,c, Overview (b) and example (c) of convergent evolution, where the same HLA allele is disrupted via different mechanisms in different regions of the same tumor. d, The relationship between the presence of repression and the amount of CD8 T cell infiltration. e, Tumor regions with and without HLA LOH have similar levels of total HLA expression. f, LUAD tumors that have HLA LOH are more likely to metastasize. g, When accounting for LOH and repression, LUAD regions that seeded a metastasis have a lower neoantigen count than those that did not. P values in d, e and g are derived from a two-sided Wilcoxon test. P value in f is derived from Fisher’s exact test. Boxplots in d, e and g show median and first and third quartiles, and whiskers extend up to 1.5× IQR above and below the IQR. LOH, loss of heterozygosity; rep, repression; AS, alternative splicing.