Plasma epigenomic profiling reveals treatment-emergent squamous transformation in prostate cancer

Abstract Squamous transformation of prostate adenocarcinoma is a rare resistance mechanism in patients with advanced prostate cancer that impacts both prognosis and treatment. Herein, we profile circulating chromatin in serial plasma samples collected from a patient with metastatic prostate cancer t...

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Main Authors: Karl Semaan, Rashad Nawfal, John Canniff, Hunter Savignano, Ji-Heui Seo, Stephanie E. Siegmund, Sarah J. Wu, Julia K. Rotow, Gwo-Shu Mary Lee, Razane El Hajj Chehade, Ze Zhang, Gunsagar S. Gulati, Noa Phillips, Garyoung Gary Lee, Christopher A. French, Michelle S. Hirsch, Heather A. Jacene, Atish D. Choudhury, Toni K. Choueiri, Matthew L. Freedman, Sylvan C. Baca, Jacob E. Berchuck
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:npj Precision Oncology
Online Access:https://doi.org/10.1038/s41698-025-01031-3
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author Karl Semaan
Rashad Nawfal
John Canniff
Hunter Savignano
Ji-Heui Seo
Stephanie E. Siegmund
Sarah J. Wu
Julia K. Rotow
Gwo-Shu Mary Lee
Razane El Hajj Chehade
Ze Zhang
Gunsagar S. Gulati
Noa Phillips
Garyoung Gary Lee
Christopher A. French
Michelle S. Hirsch
Heather A. Jacene
Atish D. Choudhury
Toni K. Choueiri
Matthew L. Freedman
Sylvan C. Baca
Jacob E. Berchuck
author_facet Karl Semaan
Rashad Nawfal
John Canniff
Hunter Savignano
Ji-Heui Seo
Stephanie E. Siegmund
Sarah J. Wu
Julia K. Rotow
Gwo-Shu Mary Lee
Razane El Hajj Chehade
Ze Zhang
Gunsagar S. Gulati
Noa Phillips
Garyoung Gary Lee
Christopher A. French
Michelle S. Hirsch
Heather A. Jacene
Atish D. Choudhury
Toni K. Choueiri
Matthew L. Freedman
Sylvan C. Baca
Jacob E. Berchuck
author_sort Karl Semaan
collection DOAJ
description Abstract Squamous transformation of prostate adenocarcinoma is a rare resistance mechanism in patients with advanced prostate cancer that impacts both prognosis and treatment. Herein, we profile circulating chromatin in serial plasma samples collected from a patient with metastatic prostate cancer that experienced squamous transformation. We detect dynamic changes in gene regulation from circulating chromatin reflecting the emergence of squamous differentiation, enabling non-invasive diagnosis and monitoring of this resistance phenotype, with potential therapeutic implications.
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institution Kabale University
issn 2397-768X
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publishDate 2025-07-01
publisher Nature Portfolio
record_format Article
series npj Precision Oncology
spelling doaj-art-59f3fceb99c84916b5ad6f9cf136e4c92025-08-20T04:01:42ZengNature Portfolionpj Precision Oncology2397-768X2025-07-01911710.1038/s41698-025-01031-3Plasma epigenomic profiling reveals treatment-emergent squamous transformation in prostate cancerKarl Semaan0Rashad Nawfal1John Canniff2Hunter Savignano3Ji-Heui Seo4Stephanie E. Siegmund5Sarah J. Wu6Julia K. Rotow7Gwo-Shu Mary Lee8Razane El Hajj Chehade9Ze Zhang10Gunsagar S. Gulati11Noa Phillips12Garyoung Gary Lee13Christopher A. French14Michelle S. Hirsch15Heather A. Jacene16Atish D. Choudhury17Toni K. Choueiri18Matthew L. Freedman19Sylvan C. Baca20Jacob E. Berchuck21Department of Medical Oncology, Dana-Farber Cancer InstituteDepartment of Medical Oncology, Dana-Farber Cancer InstituteDepartment of Medical Oncology, Dana-Farber Cancer InstituteDepartment of Medical Oncology, Dana-Farber Cancer InstituteDepartment of Medical Oncology, Dana-Farber Cancer InstituteDepartment of Pathology, Brigham and Women’s HospitalDepartment of Pathology, Brigham and Women’s HospitalLowe Center for Thoracic Oncology, Dana-Farber Cancer InstituteDepartment of Medical Oncology, Dana-Farber Cancer InstituteDepartment of Medical Oncology, Dana-Farber Cancer InstituteDepartment of Medical Oncology, Dana-Farber Cancer InstituteDepartment of Medical Oncology, Dana-Farber Cancer InstituteDepartment of Medical Oncology, Dana-Farber Cancer InstituteDepartment of Medical Oncology, Dana-Farber Cancer InstituteDepartment of Pathology, Brigham and Women’s HospitalDepartment of Pathology, Brigham and Women’s HospitalDepartment of Imaging, Dana-Farber Cancer InstituteDepartment of Medical Oncology, Dana-Farber Cancer InstituteDepartment of Medical Oncology, Dana-Farber Cancer InstituteDepartment of Medical Oncology, Dana-Farber Cancer InstituteDepartment of Medical Oncology, Dana-Farber Cancer InstituteDepartment of Medical Oncology, Dana-Farber Cancer InstituteAbstract Squamous transformation of prostate adenocarcinoma is a rare resistance mechanism in patients with advanced prostate cancer that impacts both prognosis and treatment. Herein, we profile circulating chromatin in serial plasma samples collected from a patient with metastatic prostate cancer that experienced squamous transformation. We detect dynamic changes in gene regulation from circulating chromatin reflecting the emergence of squamous differentiation, enabling non-invasive diagnosis and monitoring of this resistance phenotype, with potential therapeutic implications.https://doi.org/10.1038/s41698-025-01031-3
spellingShingle Karl Semaan
Rashad Nawfal
John Canniff
Hunter Savignano
Ji-Heui Seo
Stephanie E. Siegmund
Sarah J. Wu
Julia K. Rotow
Gwo-Shu Mary Lee
Razane El Hajj Chehade
Ze Zhang
Gunsagar S. Gulati
Noa Phillips
Garyoung Gary Lee
Christopher A. French
Michelle S. Hirsch
Heather A. Jacene
Atish D. Choudhury
Toni K. Choueiri
Matthew L. Freedman
Sylvan C. Baca
Jacob E. Berchuck
Plasma epigenomic profiling reveals treatment-emergent squamous transformation in prostate cancer
npj Precision Oncology
title Plasma epigenomic profiling reveals treatment-emergent squamous transformation in prostate cancer
title_full Plasma epigenomic profiling reveals treatment-emergent squamous transformation in prostate cancer
title_fullStr Plasma epigenomic profiling reveals treatment-emergent squamous transformation in prostate cancer
title_full_unstemmed Plasma epigenomic profiling reveals treatment-emergent squamous transformation in prostate cancer
title_short Plasma epigenomic profiling reveals treatment-emergent squamous transformation in prostate cancer
title_sort plasma epigenomic profiling reveals treatment emergent squamous transformation in prostate cancer
url https://doi.org/10.1038/s41698-025-01031-3
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