Volume 19, Issue 11, Pages (June 2017)

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Volume 19, Issue 11, Pages 2185-2192 (June 2017) Enhanced Rate of Acquisition of Point Mutations in Mouse Intestinal Adenomas Compared to Normal Tissue Natalia Lugli, Vasilis S. Dionellis, Paloma Ordóñez-Morán, Irene Kamileri, Sotirios K. Sotiriou, Joerg Huelsken, Thanos D. Halazonetis Cell Reports Volume 19, Issue 11, Pages 2185-2192 (June 2017) DOI: 10.1016/j.celrep.2017.05.051 Copyright © 2017 The Author(s) Terms and Conditions

Cell Reports 2017 19, 2185-2192DOI: (10.1016/j.celrep.2017.05.051) Copyright © 2017 The Author(s) Terms and Conditions

Figure 1 Growth of Small Intestine Single-Cell-Derived Organoids (A and B) Phase-contrast images of small intestine normal (A) and tumor-derived (B) organoids. Scale bars, 200 μm. (C and D) Immunofluorescence staining for γH2AX (red) in small intestine normal (C) and tumor-derived (D) organoids. Scale bars, 20 μm. Nuclei were counterstained with DAPI (blue). Cell Reports 2017 19, 2185-2192DOI: (10.1016/j.celrep.2017.05.051) Copyright © 2017 The Author(s) Terms and Conditions

Figure 2 SNSs in Normal and Tumor-Derived Organoids (A) Number of SNSs in 7 normal (N) and 15 tumor-derived (T) organoids from three Apcmin/+ mice after 1 month in culture. Distinct tumors are labeled T1, T2, etc., and crypts from these tumors are labeled A, B, etc. Mice are labeled by roman numerals. Overlaps indicate the number of shared SNSs. (B) Number of SNSs in two normal (N) and two tumor-derived (T) organoids after 1 and 4 months (m1 and m4, respectively) in tissue culture. Overlaps indicate the number of shared SNSs. (C) Allele frequencies of the SNSs. Green or orange dots depict SNSs detected after 1 or 4 months of in vitro culture, respectively. Cell Reports 2017 19, 2185-2192DOI: (10.1016/j.celrep.2017.05.051) Copyright © 2017 The Author(s) Terms and Conditions

Figure 3 Mutational Signatures (A and B) Mutational signatures of normal (N) and tumor-derived (T) small-intestine organoids after 1 month (A) or 4 months (B) in culture. Cell Reports 2017 19, 2185-2192DOI: (10.1016/j.celrep.2017.05.051) Copyright © 2017 The Author(s) Terms and Conditions

Figure 4 LOH in Normal and Tumor-Derived Organoids (A–C) LOH events at the APC locus that lead to loss of the wild-type allele in mice I, II, and III in (A), (B), and (C), respectively. Blue dots mark heterozygous alleles; red dots depict LOH. The entire length of chromosome 18 is depicted; liver and normal and tumor-derived organoids are compared. Further explanation of designations is given in the Figure 2 legend. Cell Reports 2017 19, 2185-2192DOI: (10.1016/j.celrep.2017.05.051) Copyright © 2017 The Author(s) Terms and Conditions