DNA secondary structures and epigenetic determinants of cancer genome evolution
MetadataShow full item record
CitationDe, Subhajyoti, and Franziska Michor. 2011. “DNA Secondary Structures and Epigenetic Determinants of Cancer Genome Evolution.” Nature Structural & Molecular Biology 18 (8): 950–55. https://doi.org/10.1038/nsmb.2089.
AbstractAn 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.
Citable link to this pagehttp://nrs.harvard.edu/urn-3:HUL.InstRepos:41426757
- SPH Scholarly Articles