Topography of mutational signatures in human cancer

OTLU SARITAŞ B., Díaz-Gay M., Vermes I., Bergstrom E. N., Zhivagui M., Barnes M., ...Daha Fazla

Cell Reports, cilt.42, sa.8, 2023 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 42 Sayı: 8
  • Basım Tarihi: 2023
  • Doi Numarası: 10.1016/j.celrep.2023.112930
  • Dergi Adı: Cell Reports
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chemical Abstracts Core, EMBASE, MEDLINE, Directory of Open Access Journals
  • Anahtar Kelimeler: cancer genomics, CP: Cancer, CP: Genomics, genome topography, mutational signatures, somatic mutations
  • Orta Doğu Teknik Üniversitesi Adresli: Evet

Özet

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.