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

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.

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.

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.