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Somatic mouse models of gastric cancer reveal genotype-specific features of metastatic disease

ABSTRACT: Somatic mouse models of gastric cancer reveal genotype-specific features of metastatic disease

PROVIDER: PRJNA819078 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR18456200.fastq.gz	Fastqsanger.gz
	SRR18456201.fastq.gz	Fastqsanger.gz
	SRR18456202.fastq.gz	Fastqsanger.gz
	SRR18456203.fastq.gz	Fastqsanger.gz
	SRR18456204.fastq.gz	Fastqsanger.gz

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Somatic mouse models of gastric cancer reveal genotype-specific features of metastatic disease

Project description:Metastatic gastric carcinoma is a highly lethal cancer that responds poorly to conventional and molecularly targeted therapies. Despite its clinical relevance, the mechanisms underlying the behavior and therapeutic response of this disease are poorly understood owing, in part, to a paucity of tractable models that faithfully recapitulate different subtypes of the human disease. To close this gap, we developed methods to somatically introduce different oncogenic lesions directly into the stomach epithelium and show that genotypic configurations observed in patients produce metastatic gastric cancers that recapitulate the histological, molecular, and clinical features of all non-viral molecular subtypes of the human disease. Applying this platform to both wild-type and immune-deficient mice revealed previously unappreciated links between the genotype, organotropism and immune surveillance of metastatic cells that produced distinct patterns of metastasis that were mirrored in patients. Our results establish and credential a highly portable platform for producing autochthonous cancer models with flexible genotypes and host backgrounds, which can unravel mechanisms of gastric tumorigenesis or test new therapeutic concepts aimed at improving outcomes in gastric cancer patients.

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Somatic mouse models of gastric cancer reveal genotype-specific features of metastatic disease.

Project description:Metastatic gastric carcinoma is a highly lethal cancer that responds poorly to conventional and molecularly targeted therapies. Despite its clinical relevance, the mechanisms underlying the behavior and therapeutic response of this disease are poorly understood owing, in part, to a paucity of tractable models. Here we developed methods to somatically introduce different oncogenic lesions directly into the murine gastric epithelium. Genotypic configurations observed in patients produced metastatic gastric cancers that recapitulated the histological, molecular and clinical features of all nonviral molecular subtypes of the human disease. Applying this platform to both wild-type and immunodeficient mice revealed previously unappreciated links between the genotype, organotropism and immune surveillance of metastatic cells, which produced distinct patterns of metastasis that were mirrored in patients. Our results establish a highly portable platform for generating autochthonous cancer models with flexible genotypes and host backgrounds, which can unravel mechanisms of gastric tumorigenesis or test new therapeutic concepts.

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