DNA replication timing and selection shape the landscape of nucleotide variation in cancer genomes

Yong H Woo and Wen-Hsiung Li ()
Additional contact information
Yong H Woo: The University of Chicago
Wen-Hsiung Li: The University of Chicago

Nature Communications, 2012, vol. 3, issue 1, 1-8

Abstract: Abstract Cancer cells evolve from normal cells by somatic mutations and natural selection. Comparing the evolution of cancer cells and that of organisms can elucidate the genetic basis of cancer. Here we analyse somatic mutations in >400 cancer genomes. We find that the frequency of somatic single-nucleotide variations increases with replication time during the S phase much more drastically than germ-line single-nucleotide variations and somatic large-scale structural alterations, including amplifications and deletions. The ratio of nonsynonymous to synonymous single-nucleotide variations is higher for cancer cells than for germ-line cells, suggesting weaker purifying selection against somatic mutations. Among genes with recurrent mutations only cancer driver genes show evidence of strong positive selection, and late-replicating regions are depleted of cancer driver genes, although enriched for recurrently mutated genes. These observations show that replication timing has a prominent role in shaping the single-nucleotide variation landscape of cancer cells.

Date: 2012
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/ncomms1982 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:3:y:2012:i:1:d:10.1038_ncomms1982

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms1982

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().