Mutation patterns in cancer genomes

作者：Rubin Alan F^*; Green Phil

来源：Proceedings of the National Academy of Sciences, 2009, 106(51): 21766-21770.

DOI：10.1073/pnas.0912499106

• CpG island
• dinucleotide hotspot
• mutation and selection
• mutational asymmetry

Recent large-scale cancer sequencing studies have focused primarily on identifying cancer-associated genes, but as an important byproduct provide "passenger mutation'' data that can potentially illuminate the mutational mechanisms at work in cancer cells. Here, we explore patterns of nucleotide substitution in several cancer types using published data. We first show that selection (negative or positive) has affected only a small fraction of mutations, allowing us to attribute observed trends to underlying mutational processes rather than selection. We then show that the increased CpG mutation frequency observed in some cancers primarily occurs outside of CpG islands and CpG island shores, thus rejecting the hypothesis that the increase is a byproduct of island or shore methylation followed by deamination. We observe an A -> G vs. T -> C mutational asymmetry in some cancers similar to one that has been observed in germline mutations in transcribed regions, suggesting that the mutation process may be influenced by gene expression. We also demonstrate that the relative frequency of mutations at dinucleotide "hotspots'' can be used as a tool to detect likely technical artifacts in large-scale studies.

• 出版日期2009-12-22