Comparative genomic analysis of multiple mammary tumors from a single dog: whole-genome sequencing study

BACKGROUND: Next-generation sequencing of canine spontaneous cancer is a powerful approach in both comparative oncology and veterinary genomics. We encountered a unique case with concurrent mammary tumors. Using whole-genome sequencing (WGS), we profiled the tumor-specific landscape of somatic mutations across multiple tumor subtypes, providing unprecedented evidence within an identical genetic background. RESULTS: Of the seven mammary gland tumors (MGTs) isolated, two were diagnosed as benign and five as malignant. High-quality WGS (34.5X average sequencing depth, ≥ 20X coverage across 94.9% of the genome) on tumors and a blood sample revealed missense mutations in human breast cancer-related genes such as BRCA2 and TP53. Furthermore, we found evidence of canine-specific somatic mutations depending on the tumor subtypes, including HECTD4 in malignant tumors and NIPBL in epithelial-derived malignant tumors. CONCLUSIONS: This unique case study provides novel insights into the genomic heterogeneity, clonal evolution, and subtype-specific pathogenesis of naturally occurring canine MGTs. Despite some inherent limitations and potential for individual-specific variation, our results emphasize and guide future large-scale, longitudinal studies to further elucidate the clinical and biological significance of key somatic alterations.