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. 2021 Sep 30;53(10):1434–1442. doi: 10.1038/s41588-021-00930-y

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© The Author(s) 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Extended Data Fig. 1 — Mutational signatures identified in normal intestinal crypts from individual PD44592 who had previously undergone treatment with oxaliplatin. Distinctive SBS and DBS signatures were observed that have previously been associated with oxaliplatin treatment in cancer samples. Unexpectedly high numbers of structural variants were also observed in the normal intestinal crypts from this individual and may be due to chemotherapy exposure. (a) Phylogenetic tree from individual PD44592 with structural variants (SVs) mapped to branches. Shapes correspond to SV type; translocation (circle), inversion (hexagon), large duplication (square) and deletion (triangle). Ordering of SVs and positioning along branches is arbitrary (b) SBS signature SBS35-like displayed above the Pan-Cancer Analysis of Whole Genomes (PCAWG) reference signature SBS35 (PCAWG)⁹ and E-SBS20⁴⁸ (c) Doublet Base Substitution (DBS) signature displayed above PCAWG reference signature DBS5 and E-DBS5 from Pich et al 2019⁴⁸. (d-e) Cosine similarity matrices for SBS and DBS signatures.