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

TL;DR

This study uses whole-genome sequencing to analyze multiple mammary tumors in a single dog, revealing mutations in cancer-related genes and subtype-specific genomic changes.

Contribution

The study provides novel insights into genomic heterogeneity and subtype-specific somatic mutations in naturally occurring canine mammary tumors.

Findings

Missense mutations in human breast cancer-related genes like BRCA2 and TP53 were identified in canine tumors.

Canine-specific somatic mutations were found in genes such as HECTD4 and NIPBL, depending on tumor subtype.

The study highlights genomic heterogeneity and clonal evolution in concurrent canine mammary tumors.

Abstract

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.

The online version contains supplementary material available at 10.1186/s13620-025-00311-5.

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