a NMF-derived mutational Signature “C” from XP-C tumors and tissue-matched sporadic cancers in comparison with COSMIC Signature 8 18 (Cosine similarity = 0.86). b Relative contribution of NMF-derived mutational signatures in XP-C and tissue-matched sporadic cancers (NMF approach). XP-C tumor mutational profiles are dominated by Signature “C”, while sporadic cancers by other signatures with relatively small proportion of Signature “C”. c Unsupervised hierarchical clustering based on the Cosine similarity distances between the XP-C tumors mutational profiles, NMF-derived mutational signatures from XPC tumors and tissue-matched sporadic cancers, COSMIC mutational signatures (Signatures 1−30), and XPC and Ercc1 organoid knockouts19. XP-C tumors cluster with each other and COSMIC Signature 8 forming a larger cluster with Ercc1 and XPC organoid knockouts.