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

Miklos Diossy, Viktoria Tisza, Hua Li, Pranshu Sahgal, Jia Zhou, Zsofia Sztupinszki, Denise Young, Darryl Nousome, Claire Kuo, Jiji Jiang, Yongmei Chen, Reinhard Ebner, Isabell A. Sesterhenn, Joel T. Moncur, Gregory T. Chesnut, Gyorgy Petrovics, Gregory T. Klus, Gabor Valcz, Pier Vitale Nuzzo, Dezso RibliJudit Börcsök, Aurel Prosz, Marcin Krzystanek, Thomas Ried, David Szuts, Kinza Rizwan, Salma Kaochar, Shailja Pathania, Alan D. D’Andrea, Istvan Csabai, Shiv Srivastava, Matthew L. Freedman*, Albert Dobi*, Sandor Spisak*, Zoltan Szallasi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number208
Journalnpj Precision Oncology
Volume8
Issue number1
DOIs
StatePublished - Dec 2024
Externally publishedYes

Cite this