Topography of mutational signatures in human cancer
Summary: 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 featu...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-08-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723009415 |
| _version_ | 1827855620083023872 |
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| author | Burçak Otlu Marcos Díaz-Gay Ian Vermes Erik N. Bergstrom Maria Zhivagui Mark Barnes Ludmil B. Alexandrov |
| author_facet | Burçak Otlu Marcos Díaz-Gay Ian Vermes Erik N. Bergstrom Maria Zhivagui Mark Barnes Ludmil B. Alexandrov |
| author_sort | Burçak Otlu |
| collection | DOAJ |
| description | Summary: 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. |
| first_indexed | 2024-03-12T11:53:14Z |
| format | Article |
| id | doaj.art-2bad3d2278f34f4d858be7fc84bbc8cd |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-03-12T11:53:14Z |
| publishDate | 2023-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-2bad3d2278f34f4d858be7fc84bbc8cd2023-08-31T05:02:13ZengElsevierCell Reports2211-12472023-08-01428112930Topography of mutational signatures in human cancerBurçak Otlu0Marcos Díaz-Gay1Ian Vermes2Erik N. Bergstrom3Maria Zhivagui4Mark Barnes5Ludmil B. Alexandrov6Department of Cellular and Molecular Medicine, UC San Diego, La Jolla, CA 92093, USA; Department of Bioengineering, UC San Diego, La Jolla, CA 92093, USA; Moores Cancer Center, UC San Diego, La Jolla, CA 92037, USA; Department of Health Informatics, Graduate School of Informatics, Middle East Technical University, Ankara 06800, TurkeyDepartment of Cellular and Molecular Medicine, UC San Diego, La Jolla, CA 92093, USA; Department of Bioengineering, UC San Diego, La Jolla, CA 92093, USA; Moores Cancer Center, UC San Diego, La Jolla, CA 92037, USACOSMIC, Wellcome Sanger Institute, Hinxton, Cambridgeshire CB10 1SA, UKDepartment of Cellular and Molecular Medicine, UC San Diego, La Jolla, CA 92093, USA; Department of Bioengineering, UC San Diego, La Jolla, CA 92093, USA; Moores Cancer Center, UC San Diego, La Jolla, CA 92037, USADepartment of Cellular and Molecular Medicine, UC San Diego, La Jolla, CA 92093, USA; Department of Bioengineering, UC San Diego, La Jolla, CA 92093, USA; Moores Cancer Center, UC San Diego, La Jolla, CA 92037, USADepartment of Cellular and Molecular Medicine, UC San Diego, La Jolla, CA 92093, USA; Department of Bioengineering, UC San Diego, La Jolla, CA 92093, USA; Moores Cancer Center, UC San Diego, La Jolla, CA 92037, USADepartment of Cellular and Molecular Medicine, UC San Diego, La Jolla, CA 92093, USA; Department of Bioengineering, UC San Diego, La Jolla, CA 92093, USA; Moores Cancer Center, UC San Diego, La Jolla, CA 92037, USA; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124723009415CP: CancerCP: Genomics |
| spellingShingle | Burçak Otlu Marcos Díaz-Gay Ian Vermes Erik N. Bergstrom Maria Zhivagui Mark Barnes Ludmil B. Alexandrov Topography of mutational signatures in human cancer Cell Reports CP: Cancer CP: Genomics |
| title | Topography of mutational signatures in human cancer |
| title_full | Topography of mutational signatures in human cancer |
| title_fullStr | Topography of mutational signatures in human cancer |
| title_full_unstemmed | Topography of mutational signatures in human cancer |
| title_short | Topography of mutational signatures in human cancer |
| title_sort | topography of mutational signatures in human cancer |
| topic | CP: Cancer CP: Genomics |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723009415 |
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