  The rapid growth of cancer genome structural information provides an
opportunity for a better understanding of the mutational mechanisms of genomic
alterations in cancer and the forces of selection that act upon them. Here we
test the evidence for two major forces, spatial chromosome structure and
purifying (or negative) selection, that shape the landscape of somatic
copy-number alterations (SCNAs) in cancer1. Using a maximum likelihood
framework 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 (FG) model2. This analysis provides evidence
that the distribution of chromosomal alterations in cancer is spatially related
to three-dimensional genomic architecture and additionally suggests that
purifying selection as well as positive selection shapes the landscape of SCNAs
during somatic evolution of cancer cells.
