Publication Date

9-19-2024

Journal

npj Precision Oncology

DOI

10.1038/s41698-024-00705-8

PMID

39294262

PMCID

PMC11411125

PubMedCentral® Posted Date

9-19-2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Prognostic markers, Cancer, Computational biology and bioinformatics

Abstract

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.

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