npj Precision Oncology (Sep 2024)
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 Ribli,
- Judit 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
Affiliations
- Miklos Diossy
- Danish Cancer Institute
- Viktoria Tisza
- Computational Health Informatics Program, Boston Children’s Hospital, Harvard Medical School
- Hua Li
- Center for Prostate Disease Research, Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences
- Pranshu Sahgal
- Computational Health Informatics Program, Boston Children’s Hospital, Harvard Medical School
- Jia Zhou
- Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School
- Zsofia Sztupinszki
- Danish Cancer Institute
- Denise Young
- Center for Prostate Disease Research, Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences
- Darryl Nousome
- Center for Prostate Disease Research, Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences
- Claire Kuo
- Center for Prostate Disease Research, Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences
- Jiji Jiang
- Center for Prostate Disease Research, Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences
- Yongmei Chen
- Center for Prostate Disease Research, Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences
- Reinhard Ebner
- CytoTest Inc.
- Isabell A. Sesterhenn
- Joint Pathology Center
- Joel T. Moncur
- Joint Pathology Center
- Gregory T. Chesnut
- Center for Prostate Disease Research, Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences
- Gyorgy Petrovics
- Center for Prostate Disease Research, Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences
- Gregory T. Klus
- Computational Health Informatics Program, Boston Children’s Hospital, Harvard Medical School
- Gabor Valcz
- MTA-SE Molecular Medicine Research Group, Hungarian Academy of Sciences
- Pier Vitale Nuzzo
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School
- Dezso Ribli
- Department of Physics of Complex Systems, Eötvös Loránd University
- Judit Börcsök
- Danish Cancer Institute
- Aurel Prosz
- Danish Cancer Institute
- Marcin Krzystanek
- Danish Cancer Institute
- Thomas Ried
- Genetics Branch, Center for Cancer Research, National Cancer Institute
- David Szuts
- Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences
- Kinza Rizwan
- Department of Medicine, Baylor College of Medicine
- Salma Kaochar
- Department of Medicine, Baylor College of Medicine
- Shailja Pathania
- Center for Personalized Cancer Therapy, University of Massachusetts
- Alan D. D’Andrea
- Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School
- Istvan Csabai
- Department of Physics of Complex Systems, Eötvös Loránd University
- Shiv Srivastava
- Center for Prostate Disease Research, Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences
- Matthew L. Freedman
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School
- Albert Dobi
- Center for Prostate Disease Research, Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences
- Sandor Spisak
- Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences
- Zoltan Szallasi
- Danish Cancer Institute
- DOI
- https://doi.org/10.1038/s41698-024-00705-8
- Journal volume & issue
-
Vol. 8,
no. 1
pp. 1 – 13
Abstract
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.
