Navonil De Sarkar, Robert D Patton, Anna-Lisa Doebley, Brian Hanratty, Mohamed Adil, Adam J Kreitzman, Jay F Sarthy, Minjeong Ko, Sandipan Brahma, Michael P Meers, Derek H Janssens, Lisa S Ang, Ilsa M Coleman, Arnab Bose, Ruth F Dumpit, Jared M Lucas, Talina A Nunez, Holly M Nguyen, Heather M McClure, Colin C Pritchard, Michael T Schweizer, Colm Morrissey, Atish D Choudhury, Sylvan C Baca, Jacob E Berchuck, Matthew L Freedman, Kami Ahmad, Michael C Haffner, R Bruce Montgomery, Eva Corey, Steven Henikoff, Peter S Nelson, Gavin Ha
Advanced prostate cancers comprise distinct phenotypes, but tumor classification remains clinically challenging. Here, we harnessed circulating tumor DNA (ctDNA) to study tumor phenotypes by ascertaining nucleosome positioning patterns associated with transcription regulation. We sequenced plasma ctDNA whole genomes from patient-derived xenografts representing a spectrum of androgen receptor active (ARPC) and neuroendocrine (NEPC) prostate cancers. Nucleosome patterns associated with transcriptional activity were reflected in ctDNA at regions of genes, promoters, histone modifications, transcription factor binding, and accessible chromatin...
November 18, 2022: Cancer Discovery