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Temporal evolution of cellular heterogeneity during the progression to advanced, AR-negative prostate cancer

ABSTRACT: Temporal evolution of cellular heterogeneity during the progression to advanced, AR-negative prostate cancer

PROVIDER: PRJNA635801 | ENA |

REPOSITORIES: ENA

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Dataset's files

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			Action	DRS
	SRR11873741.fastq.gz	Fastqsanger.gz
	SRR11873742.fastq.gz	Fastqsanger.gz
	SRR11873743.fastq.gz	Fastqsanger.gz
	SRR11873744.fastq.gz	Fastqsanger.gz
	SRR11873745.fastq.gz	Fastqsanger.gz

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Project description:Despite advances in the development of highly effective androgen receptor (AR)-directed therapies for the treatment of men with advanced prostate cancer, acquired resistance ultimately ensues. A significant subset of patients with resistant disease develop AR-null, androgen-indifferent tumors that lose their luminal identify and display neuroendocrine features (neuroendocrine prostate cancer (NEPC)). Utilizing a genetically engineered mouse model, we have characterized the synergy between N-Myc overexpression and RB1 loss-of-function which results in the formation of AR-negative, poorly differentiated tumors with high metastatic potential. Single-cell-based approaches revealed striking changes to the transcriptome and chromatin accessibility during the transition to NEPC. Global DNA methylation and the N-Myc cistrome are redirected following RB1 loss. Altogether, our data provide new insight into the progression to NEPC.

2021-04-07 | GSE151581 | GEO