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Credits
- Chennan Li, Anna Baj
- Clara C. Y. Seo
- Nicholas T. Terrigino
- John R. Bright
- S. Thomas Hennigan
- Isaiah M. King
- Scott Wilkinson
- Tzu-Ting Huang
- Shana Y. Trostel
- William D. Figg
- William L. Dahut
- David Y. Takeda
- Jung-Min Lee
- Fatima Karzai
- Adam G. Sowalsky
Serial plasma dual 5mC/5hmC profiling moved liquid biopsy beyond mutation detection toward transcriptome-like tumor-state and resistance monitoring in mCRPC
Why This Study
Phase 2 cohort with serial plasma collection
Genomics alone was prognostic but biologically incomplete; only a few recurrent baseline features showed associations with outcomes
Assay Logic
In ctDNA, promoter 5mC falls while gene body 5hmC rises at active tumor genes
Validation
Composite 5hmC + 5mC background-corrected, purity-adjusted Z-score tracked with gene expression better than either mark alone
Applied to baseline cfDNA, dual 5mC/5hmC recovered expected lineage states driven by androgen receptor, neuroendocrine and double-negative programs
Baseline Biology
Poor responders showed a WNT5A-linked, less inflamed state
Longitudinal Resistance
Two resistance routes emerged on longitudinal profiling
