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Genome Organization in Cancer Cells

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Abstract

Tumor cells display dramatic changes in gene expression compared to the normal cells in the surrounding tissue. These changes are often due to chromosomal rearrangements or somatic mutations which result in the altered expression or function of proteins that regulate transcription. Indeed, recurrent chromosomal translocations are hallmarks of human cancers and vary between different types of cancer. Recent studies have implicated genome organization and the frequency of DNA double strand breaks as important factors contributing to the formation of specific chromosomal translocations. It has also become increasingly clear that nonrandom organization of the genome regulates gene expression in a cell type-specific manner. Single nucleotide changes in intergenic regions of the genome have been shown to affect gene regulation through the formation of chromatin loops. Therefore, understanding the interplay between genome organization and transcription in normal cell types and its perturbations in cancer will provide important insights into the causes of tumorigenesis.

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Abbreviations

AID:

Activation-induced cytidine deaminase

DSBs:

DNA double-strand breaks

FISH:

Fluorescence in situ hybridization

GWAS:

Genome-wide association studies

H3K4me3:

Histone H3 lysine4 trimethylation

H3K9ac:

Histone H3 lysine 9 acetylation

H3K9me2:

Histone H3 lysine 9 dimethylation

H3K9me3:

Histone H3 lysine 9 trimethylation

H4K20me3:

Histone H4 lysine 20 trimethylation

Ig:

Immunoglobulin locus

ISH:

In situ hybridisation

RNAPI:

RNA polymerase I

RNAPII:

RNA polymerase II

RNAPIII:

RNA polymerase III

rRNA:

Ribosomal RNA

SNPs:

Single nucleotide polymorphisms

TCR:

T-cell receptor locus

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Acknowledgment 

This work was supported by Canada Foundation for Innovation, Canadian Institutes of Health Research, and the Ontario Ministry of Economic Development and Innovation. We would like to thank members of the Mitchell lab for helpful discussions and critical review.

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Correspondence to Jennifer A. Mitchell Ph.D. .

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Zhou, H.Y., Mitchell, J.A. (2014). Genome Organization in Cancer Cells. In: Emili, A., Greenblatt, J., Wodak, S. (eds) Systems Analysis of Chromatin-Related Protein Complexes in Cancer. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-7931-4_14

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