人类基因组中的体细胞突变率在不同癌症中各不相同。通过对652个肿瘤进行比较基因组分析，Fran Supek 和Ben Lehner发现，可变DNA错配修复(MMR)是人类基因组中突变率的特征性区域差异的基础。虽然区域常染色体突变率对不同细胞类型来说基本上是稳定的，存在着与复制时机和基因表达的变化相关的差异，但携带未激活NMR的肿瘤的区域突变密度差异有所降低。因此，差异化的DNA修复而不是差异化的突变供应似乎才是人类基因组中大规模区域突变率差异的主要原因。

    原文链接：Differential DNA mismatch repair underlies mutation rate variation across the human genome

    原文摘要：Cancer genome sequencing has revealed considerable variation in somatic mutation rates across the human genome, with mutation rates elevated in heterochromatic late replicating regions and reduced in early replicating euchromatin. Multiple mechanisms have been suggested to underlie this, but the actual cause is unknown. Here we identify variable DNA mismatch repair (MMR) as the basis of this variation. Analysing ~17 million single-nucleotide variants from the genomes of 652 tumours, we show that regional autosomal mutation rates at megabase resolution are largely stable across cancer types, with differences related to changes in replication timing and gene expression. However, mutations arising after the inactivation of MMR are no longer enriched in late replicating heterochromatin relative to early replicating euchromatin. Thus, differential DNA repair and not differential mutation supply is the primary cause of the large-scale regional mutation rate variation across the human genome.