Epigenetic loss of heterogeneity from low to high grade localized prostate tumours.

Autor: Eksi SE; Cancer Early Detection Advanced Research (CEDAR), Knight Cancer Institute, OHSU, Portland, OR, 97239, USA. eksi@ohsu.edu.; Department of Biomedical Engineering, School of Medicine, OHSU, Portland, OR, 97209, USA. eksi@ohsu.edu., Chitsazan A; Cancer Early Detection Advanced Research (CEDAR), Knight Cancer Institute, OHSU, Portland, OR, 97239, USA., Sayar Z; Cancer Early Detection Advanced Research (CEDAR), Knight Cancer Institute, OHSU, Portland, OR, 97239, USA.; Department of Biomedical Engineering, School of Medicine, OHSU, Portland, OR, 97209, USA., Thomas GV; Cancer Early Detection Advanced Research (CEDAR), Knight Cancer Institute, OHSU, Portland, OR, 97239, USA.; Department of Pathology & Laboratory Medicine, School of Medicine, OHSU, Portland, OR, 97239, USA., Fields AJ; Department of Molecular and Medical Genetics, School of Medicine, OHSU, Portland, OR, 97239, USA., Kopp RP; Department of Urology, School of Medicine, OHSU, Portland, OR, 97239, USA., Spellman PT; Cancer Early Detection Advanced Research (CEDAR), Knight Cancer Institute, OHSU, Portland, OR, 97239, USA.; Department of Molecular and Medical Genetics, School of Medicine, OHSU, Portland, OR, 97239, USA., Adey AC; Cancer Early Detection Advanced Research (CEDAR), Knight Cancer Institute, OHSU, Portland, OR, 97239, USA. adey@ohsu.edu.; Department of Molecular and Medical Genetics, School of Medicine, OHSU, Portland, OR, 97239, USA. adey@ohsu.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2021 Dec 15; Vol. 12 (1), pp. 7292. Date of Electronic Publication: 2021 Dec 15.
DOI: 10.1038/s41467-021-27615-8
Abstrakt: Identifying precise molecular subtypes attributable to specific stages of localized prostate cancer has proven difficult due to high levels of heterogeneity. Bulk assays represent a population-average, which mask the heterogeneity that exists at the single-cell level. In this work, we sequence the accessible chromatin regions of 14,424 single-cells from 18 flash-frozen prostate tumours. We observe shared chromatin features among low-grade prostate cancer cells are lost in high-grade tumours. Despite this loss, high-grade tumours exhibit an enrichment for FOXA1, HOXB13 and CDX2 transcription factor binding sites, indicating a shared trans-regulatory programme. We identify two unique genes encoding neuronal adhesion molecules that are highly accessible in high-grade prostate tumours. We show NRXN1 and NLGN1 expression in epithelial, endothelial, immune and neuronal cells in prostate cancer using cyclic immunofluorescence. Our results provide a deeper understanding of the active gene regulatory networks in primary prostate tumours, critical for molecular stratification of the disease.
(© 2021. The Author(s).)
Databáze: MEDLINE
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