Personalized genomic landscape of prostate cancer in African American men reveals novel drivers and therapeutic opportunities
5 affiliations
- 1Department of Biochemistry & Molecular Cell Biology, Georgetown University Medical Center, Washington, District of Columbia, United States of America
- 2Department of Genetics, Yale University School of Medicine, New Haven, Connecticut, United States of America
- 3Department of Urology, Georgetown University School of Medicine, Washington, District of Columbia, United States of America
- 4MedStar Georgetown University Hospital, Washington, District of Columbia, United States of America
- 5Department of Radiation Medicine, Georgetown University School of Medicine, Washington, District of Columbia, United States of America
Abstract
African American (AA) men experience disproportionately high prostate cancer incidence and mortality. Despite this disparity, current genomic repositories are predominantly derived from European populations, and studies using archived tissues are often limited by stromal contamination. We sought to characterize the high-resolution somatic mutational landscape of AA prostate cancer using a high-fidelity, patient-matched model system to identify population-specific drivers and therapeutic targets. We performed whole-genome sequencing (WGS) on 10 matched pairs of primary cell cultures derived from prostate tumors and adjacent non-malignant tissues of AA patients. Our analyses revealed a complex, heterogeneous landscape characterized by significant genomic instability, including frequent chromothripsis and kataegis signatures. Mutation hotspots were concentrated on chromosomes 1, 2, 3, and X, with the highest mutation density on chromosome 17. Functionally impactful mutations were identified in critical oncogenic pathways, including chromatin remodeling (CHD1, ARID1A, ATRX, KDM6A) and DNA damage response (ATM, BRCA1/2, RAD51). Additionally, we identified potentially novel candidate mutations unique to this AA cohort, distinct from those in European-centric datasets. This study provides a foundational, patient-specific WGS dataset derived from African American prostate cancer cell models. The identification of high-frequency actionable alterations in epigenetic and DNA repair pathways highlights the utility of this renewable resource for developing tailored therapeutic interventions and addressing racial disparities in prostate cancer outcomes.
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BibTeX
@article{murthy2026personalized,
title = {{Personalized genomic landscape of prostate cancer in African American men reveals novel drivers and therapeutic opportunities}},
author = {Shanta Murthy and Katie Fago and James Knight and Keith Kowalczyk and Ryan Hankins and Gaurav Bandi and Anatoly Dritschilo and Mira Jung},
journal = {PLOS One},
year = {2026},
month = oct,
doi = {10.1371/journal.pone.0360389},
url = {https://doi.org/10.1371/journal.pone.0360389},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Personalized genomic landscape of prostate cancer in African American men reveals novel drivers and therapeutic opportunities
AU - Shanta Murthy
AU - Katie Fago
AU - James Knight
AU - Keith Kowalczyk
AU - Ryan Hankins
AU - Gaurav Bandi
AU - Anatoly Dritschilo
AU - Mira Jung
PY - 2026
DA - 2026/10/14
JO - PLOS One
DO - 10.1371/journal.pone.0360389
UR - https://doi.org/10.1371/journal.pone.0360389
AB - African American (AA) men experience disproportionately high prostate cancer incidence and mortality. Despite this disparity, current genomic repositories are predominantly derived from European populations, and studies using archived tissues are often limited by stromal contamination. We sought to characterize the high-resolution somatic mutational landscape of AA prostate cancer using a high-fidelity, patient-matched model system to identify population-specific drivers and therapeutic targets. We performed whole-genome sequencing (WGS) on 10 matched pairs of primary cell cultures derived from prostate tumors and adjacent non-malignant tissues of AA patients. Our analyses revealed a complex, heterogeneous landscape characterized by significant genomic instability, including frequent chromothripsis and kataegis signatures. Mutation hotspots were concentrated on chromosomes 1, 2, 3, and X, with the highest mutation density on chromosome 17. Functionally impactful mutations were identified in critical oncogenic pathways, including chromatin remodeling (CHD1, ARID1A, ATRX, KDM6A) and DNA damage response (ATM, BRCA1/2, RAD51). Additionally, we identified potentially novel candidate mutations unique to this AA cohort, distinct from those in European-centric datasets. This study provides a foundational, patient-specific WGS dataset derived from African American prostate cancer cell models. The identification of high-frequency actionable alterations in epigenetic and DNA repair pathways highlights the utility of this renewable resource for developing tailored therapeutic interventions and addressing racial disparities in prostate cancer outcomes.
SN - 1932-6203
ER -