High-order chromatin architecture determines the landscape of chromosomal alterations in cancer
Author(s)Fudenberg, Geoffrey; Getz, Gad; Meyerson, Matthew L.; Mirny, Leonid A.
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The accumulation of data on structural variation in cancer genomes provides an opportunity to better understand the mechanisms of genomic alterations and the forces of selection that act upon these alterations in cancer. Here we test evidence supporting the influence of two major forces, spatial chromosome structure and purifying (or negative) selection, on the landscape of somatic copy-number alterations (SCNAs) in cancer[superscript 1]. Using a maximum likelihood approach, we compare SCNA maps and three-dimensional genome architecture as determined by genome-wide chromosome conformation capture (HiC) and described by the proposed fractal-globule model[superscript 2, 3]. This analysis suggests that the distribution of chromosomal alterations in cancer is spatially related to three-dimensional genomic architecture and that purifying selection, as well as positive selection, influences SCNAs during somatic evolution of cancer cells.
Author Manuscript 2012 June 01.
DepartmentHarvard University--MIT Division of Health Sciences and Technology; Massachusetts Institute of Technology. Department of Physics; Massachusetts Institute of Technology. School of Engineering
Nature Publishing Group
Fudenberg, Geoff et al. “High Order Chromatin Architecture Shapes the Landscape of Chromosomal Alterations in Cancer.” Nature Biotechnology 29.12 (2011): 1109–1113.
Author's final manuscript