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Sökning: (WFRF:(Umer Husen Muhammad)) > (2021)

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  • Umer, Husen Muhammad, et al. (författare)
  • Functional annotation of noncoding mutations in cancer
  • 2021
  • Ingår i: Life Science Alliance. - : Life Science Alliance, LLC. - 2575-1077. ; 4:9
  • Tidskriftsartikel (refereegranskat)abstract
    • In a cancer genome, the noncoding sequence contains the vast majority of somatic mutations. While very few are expected to be cancer drivers, those affecting regulatory elements have the potential to have downstream effects on gene regulation that may contribute to cancer progression. To prioritize regulatory mutations, we screened somatic mutations in the Pan-Cancer Analysis of Whole Genomes cohort of 2,515 cancer genomes on individual bases to assess their potential regulatory roles in their respective cancer types. We found a highly significant enrichment of regulatory mutations associated with the deamination signature overlapping a CpG site in the CCAAT/Enhancer Binding Protein beta recognition sites in many cancer types. Overall, 5,749 mutated regulatory elements were identified in 1,844 tumor samples from 39 cohorts containing 11,962 candidate regulatory mutations. Our analysis indicated 20 or more regulatory mutations in 5.5% of the samples, and an overall average of six per tumor. Several recurrent elements were identified, and major cancer-related pathways were significantly enriched for genes nearby the mutated regulatory elements. Our results provide a detailed view of the role of regulatory elements in cancer genomes.
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