Multiomic analysis of homologous recombination-deficient end-stage high-grade serous ovarian cancer.
Journal
Nature genetics
ISSN: 1546-1718
Titre abrégé: Nat Genet
Pays: United States
ID NLM: 9216904
Informations de publication
Date de publication:
03 2023
03 2023
Historique:
received:
22
11
2021
accepted:
26
01
2023
pubmed:
1
3
2023
medline:
16
3
2023
entrez:
28
2
2023
Statut:
ppublish
Résumé
High-grade serous ovarian cancer (HGSC) is frequently characterized by homologous recombination (HR) DNA repair deficiency and, while most such tumors are sensitive to initial treatment, acquired resistance is common. We undertook a multiomics approach to interrogate molecular diversity in end-stage disease, using multiple autopsy samples collected from 15 women with HR-deficient HGSC. Patients had polyclonal disease, and several resistance mechanisms were identified within most patients, including reversion mutations and HR restoration by other means. We also observed frequent whole-genome duplication and global changes in immune composition with evidence of immune escape. This analysis highlights diverse evolutionary changes within HGSC that evade therapy and ultimately overwhelm individual patients.
Identifiants
pubmed: 36849657
doi: 10.1038/s41588-023-01320-2
pii: 10.1038/s41588-023-01320-2
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
437-450Subventions
Organisme : U.S. Department of Defense (United States Department of Defense)
ID : HU0001-16-2-0006
Organisme : U.S. Department of Defense (United States Department of Defense)
ID : HU0001-16-2-0014
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.
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