Harvard University, Program in Biophysics, Boston, Massachusetts, USA.
Nat Biotechnol. 2011 Nov 20;29(12):1109-13. doi: 10.1038/nbt.2049.
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.
癌症基因组结构变异数据的积累为更好地理解基因组改变的机制以及这些改变在癌症中受到的选择压力提供了机会。在这里，我们检验了两种主要力量（空间染色体结构和净化（或负）选择）对癌症中体细 胞拷贝数改变（SCNAs）景观的影响的证据。我们使用最大似然法，比较了 SCNAs 图谱和全基因组染色体构象捕获（HiC）确定的三维基因组结构以及提出的分形球模型所描述的三维基因组结构。该分析表明，癌症中染色体改变的分布与三维基因组结构在空间上相关，净化选择以及阳性选择均会影响癌细胞体细 胞进化过程中的 SCNAs。
