Nucleosome Patterns in Circulating Tumor DNA Reveal Transcriptional Regulation of Advanced Prostate Cancer Phenotypes.

Autor:	De Sarkar N; Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, Washington.; Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, Washington.; Division of Clinical Research, Fred Hutchinson Cancer Center, Seattle, Washington.; Department of Pathology and Prostate Cancer Center of Excellence, Medical College of Wisconsin, Milwaukee, Wisconsin., Patton RD; Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, Washington.; Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, Washington., Doebley AL; Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, Washington.; Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, Washington.; Molecular and Cellular Biology Graduate Program, University of Washington, Seattle, Washington.; Medical Scientist Training Program, University of Washington, Seattle, Washington., Hanratty B; Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, Washington., Adil M; Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, Washington., Kreitzman AJ; Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, Washington.; Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, Washington., Sarthy JF; Division of Basic Sciences, Fred Hutchinson Cancer Center, Seattle, Washington., Ko M; Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, Washington.; Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, Washington., Brahma S; Division of Basic Sciences, Fred Hutchinson Cancer Center, Seattle, Washington., Meers MP; Division of Basic Sciences, Fred Hutchinson Cancer Center, Seattle, Washington., Janssens DH; Division of Basic Sciences, Fred Hutchinson Cancer Center, Seattle, Washington., Ang LS; Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, Washington., Coleman IM; Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, Washington., Bose A; Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, Washington., Dumpit RF; Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, Washington., Lucas JM; Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, Washington., Nunez TA; Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, Washington., Nguyen HM; Department of Urology, University of Washington, Seattle, Washington., McClure HM; Dana-Farber Cancer Institute, Boston, Massachusetts., Pritchard CC; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington.; Brotman Baty Institute for Precision Medicine, Seattle, Washington., Schweizer MT; Division of Clinical Research, Fred Hutchinson Cancer Center, Seattle, Washington.; Division of Oncology, Department of Medicine, University of Washington, Seattle, Washington., Morrissey C; Department of Urology, University of Washington, Seattle, Washington., Choudhury AD; Dana-Farber Cancer Institute, Boston, Massachusetts.; Broad Institute of MIT and Harvard, Cambridge, Massachusetts., Baca SC; Dana-Farber Cancer Institute, Boston, Massachusetts.; Broad Institute of MIT and Harvard, Cambridge, Massachusetts., Berchuck JE; Dana-Farber Cancer Institute, Boston, Massachusetts., Freedman ML; Dana-Farber Cancer Institute, Boston, Massachusetts.; Broad Institute of MIT and Harvard, Cambridge, Massachusetts., Ahmad K; Division of Basic Sciences, Fred Hutchinson Cancer Center, Seattle, Washington., Haffner MC; Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, Washington.; Division of Clinical Research, Fred Hutchinson Cancer Center, Seattle, Washington.; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington., Montgomery RB; Division of Oncology, Department of Medicine, University of Washington, Seattle, Washington., Corey E; Department of Urology, University of Washington, Seattle, Washington., Henikoff S; Division of Basic Sciences, Fred Hutchinson Cancer Center, Seattle, Washington.; Howard Hughes Medical Institute, Chevy Chase, Maryland., Nelson PS; Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, Washington.; Division of Clinical Research, Fred Hutchinson Cancer Center, Seattle, Washington.; Department of Urology, University of Washington, Seattle, Washington.; Brotman Baty Institute for Precision Medicine, Seattle, Washington.; Division of Oncology, Department of Medicine, University of Washington, Seattle, Washington., Ha G; Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, Washington.; Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, Washington.; Brotman Baty Institute for Precision Medicine, Seattle, Washington.; Department of Genome Sciences, University of Washington, Seattle, Washington.
Jazyk:	angličtina
Zdroj:	Cancer discovery [Cancer Discov] 2023 Mar 01; Vol. 13 (3), pp. 632-653.
DOI:	10.1158/2159-8290.CD-22-0692
Abstrakt:	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. We identified the activity of key phenotype-defining transcriptional regulators from ctDNA, including AR, ASCL1, HOXB13, HNF4G, and GATA2. To distinguish NEPC and ARPC in patient plasma samples, we developed prediction models that achieved accuracies of 97% for dominant phenotypes and 87% for mixed clinical phenotypes. Although phenotype classification is typically assessed by IHC or transcriptome profiling from tumor biopsies, we demonstrate that ctDNA provides comparable results with diagnostic advantages for precision oncology. Significance: This study provides insights into the dynamics of nucleosome positioning and gene regulation associated with cancer phenotypes that can be ascertained from ctDNA. New methods for classification in phenotype mixtures extend the utility of ctDNA beyond assessments of somatic DNA alterations with important implications for molecular classification and precision oncology. This article is highlighted in the In This Issue feature, p. 517. (©2022 The Authors; Published by the American Association for Cancer Research.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu