DNA replication timing and higher-order nuclear organization determine single-nucleotide substitution patterns in cancer genomes.

ABSTRACT: Single-nucleotide substitutions are a defining characteristic of cancer genomes. Many single-nucleotide substitutions in cancer genomes arise because of errors in DNA replication, which is spatio-temporally stratified. Here we propose that DNA replication patterns help shape the mutational landscapes of normal and cancer genomes. Using data on five fully sequenced cancer types and two personal genomes, we determined that the frequency of intergenic single-nucleotide substitution is significantly higher in late DNA replication timing regions, even after controlling for a number of genomic features. Furthermore, some substitution signatures are more frequent in certain DNA replication timing zones. Finally, integrating data on higher-order nuclear organization, we found that genomic regions

SUBMITTER: Liu L 

PROVIDER: S-EPMC3633418 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature