The clinical utility of integrative genomics in childhood cancer extends beyond targetable mutations.
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:
27
06
2022
accepted:
02
11
2022
pubmed:
31
12
2022
medline:
3
3
2023
entrez:
30
12
2022
Statut:
ppublish
Résumé
We conducted integrative somatic-germline analyses by deeply sequencing 864 cancer-associated genes, complete genomes and transcriptomes for 300 mostly previously treated children and adolescents/young adults with cancer of poor prognosis or with rare tumors enrolled in the SickKids Cancer Sequencing (KiCS) program. Clinically actionable variants were identified in 56% of patients. Improved diagnostic accuracy led to modified management in a subset. Therapeutically targetable variants (54% of patients) were of unanticipated timing and type, with over 20% derived from the germline. Corroborating mutational signatures (SBS3/BRCAness) in patients with germline homologous recombination defects demonstrates the potential utility of PARP inhibitors. Mutational burden was significantly elevated in 9% of patients. Sequential sampling identified changes in therapeutically targetable drivers in over one-third of patients, suggesting benefit from rebiopsy for genomic analysis at the time of relapse. Comprehensive cancer genomic profiling is useful at multiple points in the care trajectory for children and adolescents/young adults with cancer, supporting its integration into early clinical management.
Identifiants
pubmed: 36585449
doi: 10.1038/s43018-022-00474-y
pii: 10.1038/s43018-022-00474-y
pmc: PMC9970873
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
203-221Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2022. The Author(s).
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