癌症体细胞突变是多种突变和修复过程的产物，其中一些与DNA复制密切相关。已知突变率（MR）在晚复制时序（RT）区域更高，但不同过程可能影响这种关联。对来自32种肿瘤类型的2787个肿瘤样本的突变景观进行系统分析发现，约三分之一的肿瘤样本在复制时序和突变率之间呈现较弱的关联。进一步分析发现，这些样本具有独特的突变特征，并富集了与DNA复制、DNA修复和染色质结构相关的基因突变。令人惊讶的是，对弱关联组和强关联组之间的差异表达基因的分析发现，具有弱关联的肿瘤富集了与细胞间通讯和免疫系统相关的基因，提示了一种对DNA损伤的非自主响应。© 2023 Springer Nature Limited.

Cancer somatic mutations are the product of multiple mutational and repair processes, some of which are tightly associated with DNA replication. Mutation rates (MR) are known to be higher in late replication timing (RT) regions, but different processes can affect this association. Systematic analysis of the mutational landscape of 2787 tumors from 32 tumor types revealed that approximately one third of the tumor samples show weak association between replication timing and mutation rate. Further analyses revealed that those samples have unique mutational signatures and are enriched with mutations in genes involved in DNA replication, DNA repair and chromatin structure. Surprisingly, analysis of differentially expressed genes between weak and strong RT-MR association groups revealed that tumors with weak association are enriched with genes associated with cell-cell communication and the immune system, suggesting a non-autonomous response to DNA damage.© 2023. Springer Nature Limited.