Functional annotation of noncoding mutations in cancer.
Life Sci Alliance
; 4(9)2021 09.
Article
em En
| MEDLINE
| ID: mdl-34282050
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 ß 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Biologia Computacional
/
Regiões não Traduzidas
/
Genômica
/
Anotação de Sequência Molecular
/
Mutação
/
Neoplasias
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article