Comprehensive analysis of mutational signatures reveals distinct patterns and molecular processes across 27 pediatric cancers.
Journal
Nature cancer
ISSN: 2662-1347
Titre abrégé: Nat Cancer
Pays: England
ID NLM: 101761119
Informations de publication
Date de publication:
02 2023
02 2023
Historique:
received:
29
05
2021
accepted:
21
12
2022
pubmed:
27
1
2023
medline:
3
3
2023
entrez:
26
1
2023
Statut:
ppublish
Résumé
Analysis of mutational signatures can reveal underlying molecular mechanisms of the processes that have imprinted the somatic mutations found in cancer genomes. Here, we analyze single base substitutions and small insertions and deletions in pediatric cancers encompassing 785 whole-genome sequenced tumors from 27 molecularly defined cancer subtypes. We identified only a small number of mutational signatures active in pediatric cancers, compared with previously analyzed adult cancers. Further, we report a significant difference in the proportion of pediatric tumors showing homologous recombination repair defect signatures compared with previous analyses. In pediatric leukemias, we identified an indel signature, not previously reported, characterized by long insertions in nonrepeat regions, affecting mainly intronic and intergenic regions, but also exons of known cancer genes. We provide a systematic overview of COSMIC v.3 mutational signatures active across pediatric cancers, which is highly relevant for understanding tumor biology and enabling future research in defining biomarkers of treatment response.
Identifiants
pubmed: 36702933
doi: 10.1038/s43018-022-00509-4
pii: 10.1038/s43018-022-00509-4
pmc: PMC9970869
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
276-289Subventions
Organisme : NIEHS NIH HHS
ID : R01 ES032547
Pays : United States
Organisme : NIEHS NIH HHS
ID : R01 ES030993
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA269919
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2023. The Author(s).
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