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Gastrointestinal Stromal Tumor Enhancers Support a Transcription Factor Network Predictive of Clinical Outcome

ABSTRACT: Gastrointestinal Stromal Tumor Enhancers Support a Transcription Factor Network Predictive of Clinical Outcome

PROVIDER: PRJNA378612 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR5329100.fastq.gz	Fastqsanger.gz
	SRR5329110.fastq.gz	Fastqsanger.gz
	SRR5329120.fastq.gz	Fastqsanger.gz
	SRR5329130.fastq.gz	Fastqsanger.gz
	SRR5329140.fastq.gz	Fastqsanger.gz

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Gastrointestinal Stromal Tumor Enhancers Support a Transcription Factor Network Predictive of Clinical Outcome

Project description:Activating mutations in the KIT or PDGFRA receptor tyrosine kinases are hallmarks of gastrointestinal stromal tumor (GIST). The biological underpinnings of recurrence following resection or disease progression beyond kinase mutation are poorly understood. Utilizing chromatin immunoprecipitation with sequencing (ChIP-seq) of tumor samples and cell lines, we describe the enhancer landscape of GIST, highlighting genes that reinforce and extend our understanding of these neoplasms. A group of core transcription factors can be distinguished from others unique to localized and metastatic disease. The transcription factor HAND1 emerges in metastatic disease, binds to established GIST-associated enhancers and is required for GIST cell proliferation and KIT gene expression. The pattern of transcription factor expression in primary tumors is predictive of metastasis-free survival in GIST patients. These results provide insight into the enhancer landscape and transcription factor network underlying GIST, and define a new strategy for predicting clinical behavior of this disease.

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Gastrointestinal Stromal Tumor Enhancers Support a Transcription Factor Network Predictive of Clinical Outcome

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Gastrointestinal stromal tumor enhancers support a transcription factor network predictive of clinical outcome.

Project description:Activating mutations in the KIT or PDGFRA receptor tyrosine kinases are hallmarks of gastrointestinal stromal tumor (GIST). The biological underpinnings of recurrence following resection or disease progression beyond kinase mutation are poorly understood. Utilizing chromatin immunoprecipitation with sequencing of tumor samples and cell lines, we describe the enhancer landscape of GIST, highlighting genes that reinforce and extend our understanding of these neoplasms. A group of core transcription factors can be distinguished from others unique to localized and metastatic disease. The transcription factor HAND1 emerges in metastatic disease, binds to established GIST-associated enhancers, and facilitates GIST cell proliferation and KIT gene expression. The pattern of transcription factor expression in primary tumors is predictive of metastasis-free survival in GIST patients. These results provide insight into the enhancer landscape and transcription factor network underlying GIST, and define a unique strategy for predicting clinical behavior of this disease.

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Gastrointestinal Stromal Tumor Enhancers Support a Transcription Factor Network Predictive of Clinical Outcome

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

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Project description:Gastrointestinal Stromal Tumor Enhancers Support a Transcription Factor Network Predictive of Clinical Outcome

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