Satellite DNA fragility accompanies complex genome rearrangements and ecDNA oncogene amplification in canine osteosarcomas

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Canine osteosarcoma (OS) is an aggressive bone cancer with remarkable similarity to human OS. Despite its value as a comparative oncology model, the drivers of genomic instability remain poorly defined, hindering cross-species insights into disease progression. We applied long-read PacBio HiFi whole genome sequencing to matched tumor and blood samples from four purebred dogs to generate high-resolution maps of somatic structural variants (SVs). Tumor genomes showed extensive rearrangement complexity, with satellite repeat regions, particularly SAT1_CF, enriched near somatic SV breakpoints and occurring within genomic contexts marked by focal hypomethylation. We also identified multiple extrachromosomal DNA (ecDNA) elements carrying oncogenes indicating ecDNA-mediated oncogene amplification. Together, these data provide an integrated genomic and epigenomic view of canine OS, implicating satellite repeats as recurrent substrates for rearrangement and ecDNA as a prominent mode of genome remodeling. This work advances our understanding of OS genome dynamics and establishes a comparative framework for investigating repeat-driven instability and oncogene amplification across species.

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