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. 2019 Jun 28;11:42. doi: 10.1186/s13073-019-0654-6

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© The Author(s). 2019

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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Fig. 4 — Mutational signatures associated with alterations emerging during in vitro or in vivo CRC propagation. Analysis of 30 validated cancer-associated mutational signatures in hypermutated/rapidly evolving CRC cell lines. Signatures associated to MMR-deficient (6, 15, 20, 26), POLE-dependent (10), and MUTYH-associated polyposis (18) are highlighted. Analysis and clustering were performed as reported in the “Methods” section. a Heatmap of signature contributions during replication of CRC cells in vitro by analyzing alterations acquired at T90. b Heatmap of signature contributions during replication of the CRC cells in vivo by comparing xenograft tumors to the corresponding cells at T0 (see the “Methods” section for detailed information)