Nuclear organization of genomic DNA affects processes of DNA damage and repair, 
yet its effects on mutational landscapes in cancer genomes remain unclear. Here 
we analyzed genome-wide somatic mutations from 366 samples of six cancer types. 
We found that lamina-associated regions, which are typically localized at the 
nuclear periphery, displayed higher somatic mutation frequencies than did the 
interlamina regions at the nuclear core. This effect was observed even after 
adjustment for features such as GC percentage, chromatin, and replication 
timing. Furthermore, mutational signatures differed between the nuclear core and 
periphery, thus indicating differences in the patterns of DNA-damage or 
DNA-repair processes. For instance, smoking and UV-related signatures, as well 
as substitutions at certain motifs, were more enriched in the nuclear periphery. 
Thus, the nuclear architecture may influence mutational landscapes in cancer 
genomes beyond the previously described effects of chromatin structure and 
replication timing.