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. 2019 Jul 15;38(33):6109–6122. doi: 10.1038/s41388-019-0868-5

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© The Author(s) 2019

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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Fig. 1 — Recurrent high-level amplifications in CRC (a) The fraction of tumors with at least one amplification event was not associated with stage, but was substantially higher in high-ploidy tumors compared to low-ploidy tumors. b We identified a clear separation between focal and broad amplifications at approximately 15 additional copies and 50 genes in peak. Focal amplifications were distributed across multiple chromosomes (zoomed). c On five of the chromosomes with recurrent focal high-level amplifications (≥15 additional copies, <50 genes in peak), additional tumors had focal amplifications with ≥5 additional copies. Including all these amplicons, the amplification frequency was 1.5% (three tumors) for ANXA11 (10q), CCND2 (12p) and ERBB2 (17q); 2.5% (five tumors) for MYC (8q); and 3% (six tumors) for TOX3 (16q). Combined survival analysis showed that the 16 stage I-III MSS patients displaying focal amplifications (with ≥5 additional copies) in either of the five genes demonstrated a significant association to poor patient outcome. Chromosome plots: Left y-axis: number of additional copies above median copy number (different colored lines represent different tumors). Right y-axis: the percentage of samples with gain in the region of interest, visualized as a light pink band behind the lines indicating individual tumors