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β-catenin programs a tissue-specific epigenetic vulnerability in aggressive adrenocortical carcinoma (RNA-seq)

ABSTRACT: β-catenin programs a tissue-specific epigenetic vulnerability in aggressive adrenocortical carcinoma (RNA-seq)

PROVIDER: PRJNA844295 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR19503468_1.fastq.gz	Fastqsanger.gz
	SRR19503468_2.fastq.gz	Fastqsanger.gz
	SRR19503469_1.fastq.gz	Fastqsanger.gz
	SRR19503469_2.fastq.gz	Fastqsanger.gz
	SRR19503470_1.fastq.gz	Fastqsanger.gz

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β-catenin programs a tissue-specific epigenetic vulnerability in aggressive adrenocortical carcinoma

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β-catenin programs a tissue-specific epigenetic vulnerability in aggressive adrenocortical carcinoma (ATAC-seq)

Project description:Adrenocortical carcinoma (ACC) is a rare cancer in which tissue-specific differentiation is paradoxically associated with dismal outcomes. The differentiated ACC subtype CIMP-high is prevalent, incurable, and routinely fatal. CIMP-high ACC possess abnormal DNA methylation and frequent β-catenin activating mutations. Here, we demonstrate that this differentiated state is maintained by a balance between nuclear, tissue-specific β-catenin-containing complexes and the ACC epigenome. On chromatin, β-catenin binds master adrenal transcription factor SF1 and hijacks the adrenocortical super-enhancer landscape to maintain differentiation. Off chromatin, β-catenin binds histone methyltransferase EZH2, which is redistributed by the CIMP-high DNA methylation signature. SF1/β-catenin and EZH2/β-catenin complexes exist in normal adrenals and are selected for through all phases of ACC evolution. EZH2 inhibition in CIMP-high ACC favors EZH2/β-catenin assembly and purges SF1/β-catenin from chromatin, erasing differentiation and restraining cancer growth in vitro and in vivo. Our studies illustrate how tissue-specific programs shape oncogene selection, surreptitiously encoding targetable therapeutic vulnerabilities.

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β-catenin programs a tissue-specific epigenetic vulnerability in aggressive adrenocortical carcinoma (RNA-seq)

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β-catenin programs a tissue-specific epigenetic vulnerability in aggressive adrenocortical carcinoma (DNA methylation array)

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Characterization of differential gene expression in adrenocortical tumors harbouring β-catenin (CTNNB1) mutations.

Project description:Mutations of β-catenin gene (CTNNB1) are frequent in adrenocortical adenomas (AA) and carcinomas (ACC). However, the target genes of CTNNB1 have not yet been identified in adrenocortical tumors. Our objective was to identify genes de-regulated in adrenocortical tumors harbouring CTNNB1 genetic alterations.

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β-catenin programs a tissue-specific epigenetic vulnerability in aggressive adrenocortical carcinoma

Project description:This SuperSeries is composed of the SubSeries listed below.

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