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

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.

NPJ precision oncology. 2025 Jul 09*** epublish ***

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

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA., Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Department of Imaging, Dana-Farber Cancer Institute, Boston, MA, USA., Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. ., Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. .

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