| Title: |
Frequent CHD1 deletions in prostate cancers of African American men is associated with rapid disease progression |
| Authors: |
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 |
| Source: |
npj Precision Oncology, Vol 8, Iss 1, Pp 1-13 (2024) |
| Publisher Information: |
Nature Portfolio, 2024. |
| Publication Year: |
2024 |
| Collection: |
LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| Subject Terms: |
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| More Details: |
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. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2397-768X |
| Relation: |
https://doaj.org/toc/2397-768X |
| DOI: |
10.1038/s41698-024-00705-8 |
| Access URL: |
https://doaj.org/article/3508a45a6daf4e298c016ff52086528b |
| Accession Number: |
edsdoj.3508a45a6daf4e298c016ff52086528b |
| Database: |
Directory of Open Access Journals |
