Frequent CHD1 deletions in prostate cancers of African American men is associated with rapid disease progression
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.
Authors
- Shailja Pathania (ORCID: https://orcid.org/0000-0001-8974-6420)
- Sándor Spisák (ORCID: https://orcid.org/0000-0002-7834-4642)
- Gábor Valcz (ORCID: https://orcid.org/0000-0002-7109-3529)
- Isabell A. Sesterhenn (ORCID: https://orcid.org/0000-0001-9521-2097)
- Judit Börcsök (ORCID: https://orcid.org/0000-0002-3290-3971)
- Jia Zhou (ORCID: https://orcid.org/0000-0002-2156-0483)
- Zoltán Szállási (ORCID: https://orcid.org/0000-0001-5395-7509)
- Darryl Nousome (ORCID: https://orcid.org/0000-0002-5259-8599)
- Denise Young (ORCID: https://orcid.org/0000-0003-1023-6271)
- Hua Li (ORCID: https://orcid.org/0000-0002-1882-090X)
- Miklós Dióssy (ORCID: https://orcid.org/0000-0003-0308-6615)
- Jiji Jiang (ORCID: https://orcid.org/0009-0004-0629-0085)
- Marek Krzystanek (ORCID: https://orcid.org/0000-0002-1665-7344)
- Alan D. D’Andrea (ORCID: https://orcid.org/0000-0001-6168-6294)
- Gregory T. Klus
- Shiv Srivastava (ORCID: https://orcid.org/0000-0001-9014-8081)
- Huai‐Ching Kuo (ORCID: https://orcid.org/0000-0002-0777-7475)
- Pranshu Sahgal (ORCID: https://orcid.org/0000-0002-9857-3987)
- Dávid Szüts (ORCID: https://orcid.org/0000-0001-7985-0136)
- Pier Vitale Nuzzo (ORCID: https://orcid.org/0000-0002-5618-8079)
- István Csabai (ORCID: https://orcid.org/0000-0001-9232-9898)
- Salma Kaochar (ORCID: https://orcid.org/0000-0001-9437-8829)
- Dezső Ribli (ORCID: https://orcid.org/0000-0002-2709-206X)
- Viktória Tisza (ORCID: https://orcid.org/0000-0002-6254-5191)
- Zsófia Sztupinszki
- György Petrovics (ORCID: https://orcid.org/0000-0003-3732-284X)
- Gregory T. Chesnut (ORCID: https://orcid.org/0000-0002-3123-4868)
- Kinza Rizwan (ORCID: https://orcid.org/0000-0003-2147-7783)
- Matthew L. Freedman (ORCID: https://orcid.org/0000-0002-0151-1238)
- Albert Dobi (ORCID: https://orcid.org/0000-0002-0141-4577)
- Yongmei Chen (ORCID: https://orcid.org/0000-0003-1461-4890)
- Reinhard Ebner
- Joel T. Moncur
- Aurél Prósz
- Thomas Ried
Institutions
- Semmelweis University (HU)
- Eötvös Loránd University (HU)
- Broad Institute (US)
- Henry M. Jackson Foundation (US)
- Boston Children's Hospital (US)
- Harvard University (US)
- Uniformed Services University of the Health Sciences (US)
- Baylor College of Medicine (US)
- Georgetown University (US)
- University of Massachusetts Boston (US)
- Glotech (United States) (US)
- Dana-Farber Cancer Institute (US)
- Eli and Edythe Broad Foundation (US)
- National Cancer Institute (US)
- Danish Cancer Society (DK)
- Center for Cancer Research (US)
- Hungarian Academy of Sciences (HU)
- HUN-REN Research Centre for Natural Sciences (HU)
Publication Details
- Journal
- npj Precision Oncology
- Published
- 2024-09-18
- DOI
- https://doi.org/10.1038/s41698-024-00705-8
- Citations
- 4
- Primary Topic
- Prostate Cancer Treatment and Research
- Type
- article
- Field-Weighted Citation Impact
- 1.68
Funders
- U.S. Department of Defense
- Prostate Cancer Foundation
- Breast Cancer Research Foundation
- Henry M. Jackson Foundation
- Suomen Kulttuurirahasto
- Novo Nordisk
- Sigrid Juséliuksen Säätiö
- Instrumentariumin Tiedesäätiö
- Novo Nordisk Fonden
- Uniformed Services University of the Health Sciences
- National Cancer Institute
- DOD Prostate Cancer Research Program