Nature:染色质组织方式决定肿瘤细胞区域性突变率

7月22日，Nature杂志在线报道，染色质组织方式对人类癌细胞中区域性突变率具有重大影响。

癌症基因组测序，提供了人类体细胞整个基因组的基因突变率差异的第一手资料。通过检测各种遗传学和表观遗传学指标，研究者发现，癌症细胞基因组的基因突变率与染色质组织方式存在惊人的相关性。

事实上，在百万碱基数量级上，一个单一的染色质组织特性（异染色质相关组蛋白修饰H3K9me3的水平），可以导致40％以上的突变率的变化。而一系列染色质组织特性的组合因素更可导致55％以上的突变率的变化。

突变率和染色质组织之间的强烈相关性，在来源于不同组织的样本中，以及不同类型的突变中，均得到了证实。这表明将基因组序列组织成异染色质和常染色质样高级结构的方式，是人体细胞区域性突变率差异的主导因素。

doi:10.1016/j.cell.2011.10.017
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Chromatin organization is a major influence on regional mutation rates in human cancer cells

Benjamin Schuster-B?ckler& Ben Lehner

Cancer genome sequencing provides the first direct information on how mutation rates vary across the human genome in somatic cells1, 2, 3, 4, 5, 6, 7. Testing diverse genetic and epigenetic features, here we show that mutation rates in cancer genomes are strikingly related to chromatin organization. Indeed, at the megabase scale, a single feature—levels of the heterochromatin-associated histone modification H3K9me3—can account for more than 40% of mutation-rate variation, and a combination of features can account for more than 55%. The strong association between mutation rates and chromatin organization is upheld in samples from different tissues and for different mutation types. This suggests that the arrangement of the genome into heterochromatin- and euchromatin-like domains is a dominant influence on regional mutation-rate variation in human somatic cells.