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<div>Abstract<p>Chromosomal translocations and aneuploidy are hallmarks of cancer genomes; however, the impact of these aberrations on the nucleome (i.e., nuclear structure and gene expression) is not yet understood. Here, the nucleome of the colorectal cancer cell line HT-29 was analyzed using chromosome conformation capture (Hi-C) to study genome structure, complemented by RNA sequencing (RNA-seq) to determine the consequent changes in genome function. Importantly, translocations and copy number changes were identified at high resolution from Hi-C data and the structure–function relationships present in normal cells were maintained in cancer. In addition, a new copy number–based normalization method for Hi-C data was developed to analyze the effect of chromosomal aberrations on local chromatin structure. The data demonstrate that at the site of translocations, the correlation between chromatin organization and gene expression increases; thus, chromatin accessibility more directly reflects transcription. In addition, the homogeneously staining region of chromosome band 8q24 of HT-29, which includes the MYC oncogene, interacts with various loci throughout the genome and is composed of open chromatin. The methods, described herein, can be applied to the assessment of the nucleome in other cell types with chromosomal aberrations.</p><p><b>Implications:</b> Findings show that chromosome conformation capture identifies chromosomal abnormalities at high resolution in cancer cells and that these abnormalities alter the relationship between structure and function. <i>Mol Cancer Res; 15(7); 821–30. ©2017 AACR</i>.</p></div>

<p>Figure S1. Copy number based normalization method. Figure S2. Translocation 2-15 at read level. Figure S3. Translocation 3-12 at read level. Figure S4. Translocation 5-6 at read level. Figure S5. Translocation 6-14 at read level. Figure S6. Translocation 19-17 at read level. Figure S7. Translocated chromosome analysis from Hi-C data. Figure S8. Genome-wide Hi-C matrix for 2D-cultured human fibroblast cells. Figure S9. Interchromosomal matrices for translocations. Figure S10. Comparison of normalization methods. Figure S11. Normalization methods on K562 data. Figure S12. Measuring size of chromosome 8 territories. Figure S13. Interactions with the HSR for all samples. Figure S14. Interactions between the HSR and chromosome 2. Figure S15. Read level interactions between chromosomes 17 and 22 indicate there are many different translocations between the different chromosomes.</p>

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