Frequent CHD1 deletions in prostate cancers of African American men is associated with rapid disease progression

Diossy, Miklos and Tisza, Viktoria and Li, Hua and Sahgal, Pranshu and Zhou, Jia and Sztupinszki, Zsofia and Young, Denise and Nousome, Darryl and Kuo, Claire and Jiang, Jiji and Chen, Yongmei and Ebner, Reinhard and Sesterhenn, Isabell A. and Moncur, Joel T. and Chesnut, Gregory T. and Petrovics, Gyorgy and Klus, Gregory T. and Valcz, Gabor and Nuzzo, Pier Vitale and Ribli, Dezso and Börcsök, Judit and Prosz, Aurel and Krzystanek, Marcin and Ried, Thomas and Szuts, David and Rizwan, Kinza and Kaochar, Salma and Pathania, Shailja and D’Andrea, Alan D. and Csabai, Istvan and Spisák, Sándor (2024) Frequent CHD1 deletions in prostate cancers of African American men is associated with rapid disease progression. NPJ PRECISION ONCOLOGY, 8 (1). No.-208. ISSN 2397-768X

Preview

Text ProszetalNPJPrecisOncol2024.pdf - Published Version Available under License Creative Commons Attribution Non-commercial No Derivatives. Download (2MB) | Preview

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.

Actions (login required)

Edit Item