DNA secondary structures and epigenetic determinants of cancer genome evolution

被引：195

作者：

De, Subhajyoti ^{[1
,2
]}

Michor, Franziska ^{[1
,2
]}

机构：

[1] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA

[2] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA

来源：

NATURE STRUCTURAL & MOLECULAR BIOLOGY | 2011年 / 18卷 / 08期

关键词：

G-QUADRUPLEX; G4; DNA; METHYLATION CHANGES; FORMING SEQUENCES; MAMMALIAN-CELLS; GENE-EXPRESSION; TELOMERIC DNA; COPY-NUMBER; INSTABILITY; BREAST;

D O I：

10.1038/nsmb.2089

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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.

引用

页码：950 / U115

页数：7

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