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

Leibold, Josef, Amor, Corina, Tsanov, Kaloyan M, Ho, Yu-Jui, Sánchez-Rivera, Francisco J, Feucht, Judith, Baslan, Timour, Chen, Hsuan-An, Tian, Sha, Simon, Janelle, Wuest, Alexandra, Wilkinson, John E, Lowe, Scott W (June 2022) Somatic mouse models of gastric cancer reveal genotype-specific features of metastatic disease. bioRxiv. (Submitted)

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Abstract

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.

Item Type:	Paper
Subjects:	diseases & disorders > cancer diseases & disorders organism description > animal organism description > animal > mammal organism description > animal > mammal > rodent > mouse organism description > animal > mammal > rodent diseases & disorders > cancer > cancer types > stomach cancer diseases & disorders > cancer > cancer types
CSHL Authors:	Lowe, Scott W. Amor, Corina
Communities:	CSHL labs > Lowe lab
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	15 June 2022
Date Deposited:	20 Dec 2023 20:21
Last Modified:	20 Dec 2023 20:21
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/41352

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