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An epigenetic program established by gene – environment interactions initiates pancreatic carcinogenesis [Set3]

ABSTRACT: An epigenetic program established by gene – environment interactions initiates pancreatic carcinogenesis [Set3]

PROVIDER: PRJNA646636 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12235107_1.fastq.gz	Fastqsanger.gz
	SRR12235107_2.fastq.gz	Fastqsanger.gz
	SRR12235108_1.fastq.gz	Fastqsanger.gz
	SRR12235108_2.fastq.gz	Fastqsanger.gz
	SRR12235109_1.fastq.gz	Fastqsanger.gz

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Project description:Damaged tissues have increased risk of cancer development through poorly understood mechanisms. In the pancreas, tissue damage collaborates with activating mutations in the Kras oncogene to dramatically accelerate the formation of early neoplastic lesions and ultimately pancreatic cancer. By integrating genomics, single-cell chromatin assays and spatiotemporally-controlled functional perturbations in autochthonous mouse models, we show that the combination of Kras mutation and tissue damage promotes a unique chromatin state in the pancreatic epithelium that distinguishes neoplastic transformation from normal regeneration and is selected for throughout malignant evolution. This cancer-associated epigenetic state emerges within 48 hours of pancreatic injury, and involves large-scale chromatin accessibility changes that contribute to the early dysregulation of genes defining human pancreatic cancer. Among the genes most rapidly activated by tissue damage in the pre-malignant pancreatic epithelium is the alarmin cytokine IL33, which cooperates with mutant Kras in unleashing the epigenetic remodeling program of early neoplasia and neoplastic transformation in the absence of injury. Collectively, our study demonstrates how gene-environment interactions can rapidly produce gene regulatory programs that dictate early neoplastic commitment and provides a molecular framework for understanding the interplay between genetics and environmental cues in cancer initiation.

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

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