biostudies-literatureLaplante PLigue Contre le CancerMinistère de l'Enseignement Supérieur et de la RecherchePhilanthropia FoundationCampus France101145https://www.ebi.ac.uk/biostudies/studies/S-EPMC11905862biostudies-literatureUnknown62Mismatch repair deficiency leads to high mutation rates and microsatellite instability (MSI-H), associated with immune infiltration and responsiveness to immunotherapies. In early stages, MSI-H tumors generally have a better prognosis and lower metastatic potential than microsatellite-stable (MSS) tumors, especially in colorectal cancer. However, in advanced stages, MSI-H tumors lose this survival advantage for reasons that remain unclear. We developed a syngeneic mouse model of MSI cancer by knocking out the MMR gene Msh2 in the metastatic 4T1 breast cancer cell line. This model mirrored genomic features of MSI-H cancers and showed reduction in metastatic incidence compared to their MSS counterparts. In MSI-H tumors, we observed an enrichment of immune gene-signatures that negatively corrNeoplasia (New York, N.Y.)Effect of MisMatch repair deficiency on metastasis occurrence in a syngeneic mouse model.PMC1190586212551Rosa RKannouche PLLaplante PPouvelle CGoulas JNebot-Bral LNikolaev SSilvin AfalseEffect of MisMatch repair deficiency on metastasis occurrence in a syngeneic mouse model.Mismatch repair deficiency leads to high mutation rates and microsatellite instability (MSI-H), associated with immune infiltration and responsiveness to immunotherapies. In early stages, MSI-H tumors generally have a better prognosis and lower metastatic potential than microsatellite-stable (MSS) tumors, especially in colorectal cancer. However, in advanced stages, MSI-H tumors lose this survival advantage for reasons that remain unclear. We developed a syngeneic mouse model of MSI cancer by knocking out the MMR gene Msh2 in the metastatic 4T1 breast cancer cell line. This model mirrored genomic features of MSI-H cancers and showed reduction in metastatic incidence compared to their MSS counterparts. In MSI-H tumors, we observed an enrichment of immune gene-signatures that negatively corr2025-01-01T00:00:00Z2025 Apr2026-06-03T02:33:11.248Z2025-04-04T00:32:39.604ZS-EPMC119058623998591210.1016/j.neo.2025.101145