biostudies-literatureUnknownRoss CRMetastasis remains a major cause of cancer mortality. AbstractThis study, expanding upon previous findings in the MMTV-PyMT model, investigated four independent mouse models, representing luminal (MMTV-PyMT, MMTV-Myc), HER2-amplified (MMTV-Her2) and triple negative (C3(1)TAg) breast cancer subtypes. Consistent with previous results, limited evidence for metastasis-associated somatic point mutations was found for all models. We also found that oncogenic drivers significantly influenced the number and size of metastasis-specific copy number variations (MSCNVs), but common driver-independent MSCNVs were rare. Furthermore, analyzing a cohort with varying genetic backgrounds while maintaining a constant oncogenic driver (PyMT) revealed that genetic background profoundly impacts MSCNVs. TranscribioRxiv : the preprint server for biology2025.01.15.633216https://www.ebi.ac.uk/biostudies/studies/S-EPMC12478397biostudies-literatureInvestigating the genomic landscape of mouse models of breast cancer metastasis.PMC12478397Ross CRQiu THunter KWSzczepanek KSanford JPearce LfalseInvestigating the genomic landscape of mouse models of breast cancer metastasis.Metastasis remains a major cause of cancer mortality. AbstractThis study, expanding upon previous findings in the MMTV-PyMT model, investigated four independent mouse models, representing luminal (MMTV-PyMT, MMTV-Myc), HER2-amplified (MMTV-Her2) and triple negative (C3(1)TAg) breast cancer subtypes. Consistent with previous results, limited evidence for metastasis-associated somatic point mutations was found for all models. We also found that oncogenic drivers significantly influenced the number and size of metastasis-specific copy number variations (MSCNVs), but common driver-independent MSCNVs were rare. Furthermore, analyzing a cohort with varying genetic backgrounds while maintaining a constant oncogenic driver (PyMT) revealed that genetic background profoundly impacts MSCNVs. Transcri2025-01-01T00:00:00Z2025 Jan2026-05-07T03:23:29.8Z2026-05-07T03:12:55.587ZS-EPMC124783974103103810.1101/2025.01.15.633216