Frequent CHD1 deletions in prostate cancers of African American men is associated with rapid disease progression.
Journal
NPJ precision oncology
ISSN: 2397-768X
Titre abrégé: NPJ Precis Oncol
Pays: England
ID NLM: 101708166
Informations de publication
Date de publication:
19 Sep 2024
19 Sep 2024
Historique:
received:
27
02
2024
accepted:
11
09
2024
medline:
19
9
2024
pubmed:
19
9
2024
entrez:
18
9
2024
Statut:
epublish
Résumé
We analyzed genomic data from the prostate cancer of African- and European American men to identify differences contributing to racial disparity of outcome. We also performed FISH-based studies of Chromodomain helicase DNA-binding protein 1 (CHD1) loss on prostate cancer tissue microarrays. We created CHD1-deficient prostate cancer cell lines for genomic, drug sensitivity and functional homologous recombination (HR) activity analysis. Subclonal deletion of CHD1 was nearly three times as frequent in prostate tumors of African American than in European American men and it associates with rapid disease progression. CHD1 deletion was not associated with HR deficiency associated mutational signatures or HR deficiency as detected by RAD51 foci formation. This was consistent with the moderate increase of olaparib and talazoparib sensitivity with several CHD1 deficient cell lines showing talazoparib sensitivity in the clinically relevant concentration range. CHD1 loss may contribute to worse disease outcome in African American men.
Identifiants
pubmed: 39294262
doi: 10.1038/s41698-024-00705-8
pii: 10.1038/s41698-024-00705-8
doi:
Types de publication
Journal Article
Langues
eng
Pagination
208Informations de copyright
© 2024. The Author(s).
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