癌症基因组中的体细胞突变受到不同突变过程的印记。每个过程都展示出特征性的突变特征，这些特征可以受到基因组结构的影响。然而，突变特征与地形基因组特征之间的相互作用尚未得到广泛探索。在本研究中，我们将来自40种癌症类型的5,120个全基因组测序肿瘤的突变与ENCODE的516个地形特征进行整合，以评估核小体占位、组蛋白修饰、CTCF结合、复制时间和转录/复制链不对称性对不同致突变过程引起的癌症特异性突变积累的影响。大多数突变特征受到地形特征的影响，具有相关病因的突变特征同样受到影响。某些突变特征在地形特征附近表现出周期性行为或癌症类型特异性富集/减少，进一步揭示了印记它们的过程的信息。我们的研究结果通过COSMIC（癌症体细胞突变目录）突变特征数据库进行传播，提供了一个全面的在线资源，用于探索人类癌症中突变特征和地形特征之间的交互作用。版权所有 © 2023 作者。由Elsevier Inc.出版。保留所有权利。

The somatic mutations found in a cancer genome are imprinted by different mutational processes. Each process exhibits a characteristic mutational signature, which can be affected by the genome architecture. However, the interplay between mutational signatures and topographical genomic features has not been extensively explored. Here, we integrate mutations from 5,120 whole-genome-sequenced tumors from 40 cancer types with 516 topographical features from ENCODE to evaluate the effect of nucleosome occupancy, histone modifications, CTCF binding, replication timing, and transcription/replication strand asymmetries on the cancer-specific accumulation of mutations from distinct mutagenic processes. Most mutational signatures are affected by topographical features, with signatures of related etiologies being similarly affected. Certain signatures exhibit periodic behaviors or cancer-type-specific enrichments/depletions near topographical features, revealing further information about the processes that imprinted them. Our findings, disseminated via the COSMIC (Catalog of Somatic Mutations in Cancer) signatures database, provide a comprehensive online resource for exploring the interactions between mutational signatures and topographical features across human cancer.Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.