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• W2037291224 abstract "The location of DNA breakpoints associated with somatic copy-number alterations in cancer genomes is analyzed, revealing an enrichment of sequences with propensity to adopt G-quadruplex conformation, often near transcription start sites, and a correlation with hypomethylation. The analysis indicates that G4 formation contributes to cancer genome instability. An unstable genome is a hallmark of many cancers. It is unclear, however, whether some mutagenic features driving somatic alterations in cancer are encoded in the genome sequence and whether they can operate in a tissue-specific manner. We performed a genome-wide analysis of 663,446 DNA breakpoints associated with somatic copy-number alterations (SCNAs) from 2,792 cancer samples classified into 26 cancer types. Many SCNA breakpoints are spatially clustered in cancer genomes. We observed a significant enrichment for G-quadruplex sequences (G4s) in the vicinity of SCNA breakpoints and established that SCNAs show a strand bias consistent with G4-mediated structural alterations. Notably, abnormal hypomethylation near G4s-rich regions is a common signature for many SCNA breakpoint hotspots. We propose a mechanistic hypothesis that abnormal hypomethylation in genomic regions enriched for G4s acts as a mutagenic factor driving tissue-specific mutational landscapes in cancer." @default.
• W2037291224 created "2016-06-24" @default.
• W2037291224 creator A5036093562 @default.
• W2037291224 creator A5091861581 @default.
• W2037291224 date "2011-07-03" @default.
• W2037291224 modified "2023-10-18" @default.
• W2037291224 title "DNA secondary structures and epigenetic determinants of cancer genome evolution" @default.
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• W2037291224 doi "https://doi.org/10.1038/nsmb.2089" @default.
• W2037291224 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3963273" @default.
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