Variable efficiency of nonsense-mediated mRNA decay across human tissues, tumors and individuals.

However, in the case of nonsense (PTCs) mutations, we observed a difference with contrasting directions: genes with NMD-triggering PTC variants exhibited a significant trend towards higher positive selection in tumor samples with high iNMDeff, whereas tumors with low iNMDeff demonstrated less positive selection (dN/dS = 1.64 vs 1.33, p = 4.7e − 02 for ETG iNMDeff, Fig. 6 A, left panel), thereby suggesting that individual-level, global NMD efficiency can indeed shape selection on cancer genes (consistent trend in ASE iNMDeff: p = 0.13, Additional File 1: Fig.

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The borderline significance here might be attributed to the small number of SKCM patients treated with immunotherapy ( n = 73).

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