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Genomic instability

Close-up on cancer copy number alterations

Nature Reviews Genetics volume 13, page 5 (2012)Cite this article

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The SCNAs that are observed in cancer samples are a result of genomic insertions or deletions, followed by the negative selection of disadvantageous SCNAs and the positive selection of tumour-promoting SCNAs affecting oncogenes or tumour suppressor genes.

De and Michor analysed the chromosomal properties at the boundaries of >300,000 known SCNAs from ~3,000 human cancer samples of various tissue types; these boundaries represent the sites of the initiating genomic rearrangements. By comparing these sites with existing genome-wide Hi-C data of chromosomal regions that are in close three-dimensional proximity to each other and also with data on replication timing, the authors found that most cancer SCNAs involve rearrangements between sites that share long-range chromosomal interactions and have similar replication timing. This is consistent with SCNAs being initiated by sequences at replication-induced DNA breaks that are spatially and temporally coincident.

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ORIGINAL RESEARCH PAPERS

  1. De, S. & Michor, F. DNA replication timing and long-range DNA interactions predict mutational landscapes of cancer genomes. Nature Biotech. 20 Nov 2011 (doi:10.1038/nbt.2030)

  2. Fudenberg, G. et al. High order chromatin architecture shapes the landscape of chromosomal alterations in cancer. Nature Biotech. 20 Nov 2011 (doi:10.1038/nbt.2049)

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  1. Darren J. Burgess
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Burgess, D. Close-up on cancer copy number alterations. Nat Rev Genet 13, 5 (2012). https://doi.org/10.1038/nrg3133

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