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

Leibold, Josef, Tsanov, Kaloyan M, Amor, Corina, 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 (January 2024) Somatic mouse models of gastric cancer reveal genotype-specific features of metastatic disease. Nature Cancer. ISSN 2662-1347

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DOI: 10.1038/s43018-023-00686-w


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.

Item Type: Paper
Subjects: diseases & disorders > cancer
diseases & disorders
organism description > animal
organism description > animal > mammal
diseases & disorders > cancer > metastasis
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:
Communities: CSHL labs > Lowe lab
SWORD Depositor: CSHL Elements
Depositing User: CSHL Elements
Date: 4 January 2024
Date Deposited: 16 Jan 2024 18:23
Last Modified: 11 Apr 2024 14:47
PMCID: PMC10899107
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