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. 2019 Mar 8;9:3931. doi: 10.1038/s41598-019-40571-0

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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/.

PMC Copyright notice

A case study showing the clonal evolution and potential drug targets during cancer progression. (A) The clinical time course for a 66-year-old woman with pathological stage III rectal cancer at initial diagnosis. Serial genome sequencing and CT scan were tested. Nonsynonymous recurrent-specific mutated genes including DNMT3A, ERBB3, NOTCH1 were detected in recurrent tissue. FBXW7 mutations were detected in primary, recurrent tissue and cell-free DNA. (B) The clonal evolution during tumor progression. The variant allele frequency and clustering of variants with similar cellular prevalence were used to reconstruct the clonal evolution. (C) Visualizing tumor evolution with the fishplot package. The founding clone 1 (cluster 1 mutations) and the subsequent clone 2 (cluster 2 mutations) and clone 3 (cluster 3 mutations) were all detected in the recurrent tumor. Emerging NOTCH1 variant was detected in the clone 3 of recurrent tumor tissue. FBXW7 c.1745C > T was detected in cell-free DNA before the clinical evidence of recurrence.