Plasma epigenomic profiling reveals treatment-emergent squamous transformation in prostate cancer
Karl Semaan, Rashad Nawfal, John Canniff, Hunter Savignano, Ji-Heui Seo, Stephanie Siegmund, Sarah Wu, Julia 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
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.