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Fig. 4 | Genome Biology

Fig. 4

From: Negative selection in tumor genome evolution acts on essential cellular functions and the immunopeptidome

Fig. 4

Negative selection of epitopes across multiple tumor types. a We assembled lists of epitopes binding to MHC I or MHC II complexes (see “Methods”). Cells carrying mutations on native regions commonly exposed to the immune system are recognized and eliminated by immune cells. We hypothesize that the action of the immune system will leave a signature of negative selection in the cancer genome. Such evidence suggests that tumor cells may escape immune surveillance by acquiring mutations in native non-epitope regions and that native epitope regions become depleted of any high functional impact mutation. b The dN/dS ratio for both MHC I- and MHC II-binding epitopes was significantly lower than for a randomized set of non-epitope regions. The P value was computed by shuffling the coordinates of equally sized peptides within the same protein. The calculation holds when analyzing specifically patients carrying the HLA-A0201 allele vs patients not carrying this allele. c The same calculation was performed separately on MHC I and MHC II epitopes for each tumor type. Bold indicates significant when epitope-binding regions from both MHC complexes were combined. See Additional file 1: Table S1 for cancer type abbreviations. d Figure showing a negative correlation between the dN/dS ratio and the level of immune activity as measured by the quantity of local CD-8 T cells (R is the Pearson correlation coefficient). This suggests that the immune system employs a fundamental tissue-specific mechanism that drives negative selection in tumor evolution

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