title: High order chromatin architecture shapes the landscape of chromosomal alterations in cancer.
abstract: 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. 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. 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.
authors.affiliation: Harvard University, Program in Biophysics, Boston, Massachusetts, USA.
authors.forename: Geoff
authors.initials: G
authors.lastname: Fudenberg
authors.forename: Gad
authors.initials: G
authors.lastname: Getz
authors.forename: Matthew
authors.initials: M
authors.lastname: Meyerson
authors.forename: Leonid A
authors.initials: LA
authors.lastname: Mirny
mesh_terms: D000782:Aneuploidy; D002843:Chromatin / Q000737:chemistry* / Q000235:genetics; D002869:Chromosome Aberrations; D060965:Clonal Evolution / Q000235:genetics*; D056915:DNA Copy Number Variations / Q000235:genetics*; D004249:DNA Damage / Q000235:genetics; D015894:Genome, Human; D006801:Humans; D008962:Models, Theoretical; D009369:Neoplasms / Q000235:genetics*; D009690:Nucleic Acid Conformation
chemical_list: D002843:Chromatin
references.citation: Cell. 2011 Sep 30;147(1):107-19
references.pmid: 21962511
references.citation: Cell. 2011 Sep 30;147(1):95-106
references.pmid: 21962510
references.citation: Nature. 2010 Feb 18;463(7283):899-905
references.pmid: 20164920
references.citation: Nature. 2009 Apr 9;458(7239):719-24
references.pmid: 19360079
references.citation: Nature. 2011 Feb 10;470(7333):214-20
references.pmid: 21307934
references.citation: Science. 1976 Oct 1;194(4260):23-8
references.pmid: 959840
references.citation: Nature. 2007 Mar 8;446(7132):145-6
references.pmid: 17344839
references.citation: Trends Genet. 2011 Feb;27(2):63-71
references.pmid: 21144612
references.citation: Semin Cancer Biol. 2007 Feb;17(1):80-90
references.pmid: 17137790
references.citation: Chromosome Res. 2011 Jan;19(1):37-51
references.pmid: 21274616
references.citation: Cell. 2000 Nov 22;103(5):723-31
references.pmid: 11114329
references.citation: Nature. 2007 Mar 8;446(7132):153-8
references.pmid: 17344846
references.citation: Science. 2009 Oct 9;326(5950):289-93
references.pmid: 19815776
references.citation: Nat Rev Cancer. 2006 Dec;6(12):924-35
references.pmid: 17109012
references.citation: Nature. 2010 May 27;465(7297):473-7
references.pmid: 20505728
references.citation: PLoS One. 2012;7(9):e44196
references.pmid: 23028501
references.citation: BMC Cell Biol. 2005 Dec 07;6:44
references.pmid: 16336643
references.citation: Nature. 2008 Oct 23;455(7216):1061-8
references.pmid: 18772890
references.citation: Science. 2000 Oct 6;290(5489):138-41
references.pmid: 11021799
references.citation: Nat Rev Genet. 2009 Aug;10(8):551-64
references.pmid: 19597530
references.citation: PLoS Biol. 2006 May;4(5):e138
references.pmid: 16623600
references.citation: Nat Genet. 2003 Jul;34(3):287-91
references.pmid: 12808455
references.citation: Proc Natl Acad Sci U S A. 2007 Dec 11;104(50):20007-12
references.pmid: 18077431
references.citation: Science. 2007 Nov 16;318(5853):1108-13
references.pmid: 17932254