Canine mammary tumours are among the most common tumours in female dogs, representing a significant health concern due to their high prevalence and potential for malignancy. These tumours share certain clinical features with human breast cancer, making them an important subject of study for comparative oncology.
Subtypes of canine mammary tumours are genetically different
The study offers a comprehensive analysis of the genetic landscapes of the invasive ductal simple solid carcinoma and comedocarcinoma subtypes in dogs, which share similarities with human breast cancer subtypes.
Researchers utilized advanced targeted laser-capture microdissection and single-cell whole-genome sequencing techniques to reveal and compare the genetic variant landscapes of these canine mammary tumour subtypes. They found that the comedocarcinoma had six times more genetic variants than the solid carcinoma, indicating a higher level of genomic instability, malignancy, and tendency for invasion in comedocarcinoma compared with solid carcinoma.
”Discovering such significant genetic differences between these tumour subtypes opens new possibilities for understanding how distinct subtypes develop, progress, and interact with their microenvironment,” explains DVM MA Vivi Deckwirth, PhD researcher and co-first author of the study.
Bioinformatic findings contribute to understanding the genomic complexity and variations in canine mammary tumour subtypes
The study found enrichment of various biological pathways and cancer driver genes in the investigated two subtypes. Solid carcinoma showed variants in genes associated with adherens junctions and pathways such as MAPK, mTOR, and NF-kappa-B signalling.
By contrast, the comedocarcinoma was enriched with variants in pathways related to extracellular matrix receptor interaction and cell adhesion, reflecting its higher cellular malignancy.
The research identified a common driver gene in both tumour subtypes, along with subtype-distinct drivers, providing insights into their molecular mechanisms. The comedocarcinoma exhibited six times more non-silent variants and a larger number of driver genes than the solid carcinoma, indicating a greater genomic instability in comedocarcinoma.
“It is quite exciting to find such dramatic biological differences in the two subtypes of mammary tumours and several novel driver genes. Cancer driver genes are genes that contain mutations, known as driver mutations, which play a crucial role in the transformation of normal cells into cancerous cells by promoting uncontrolled cell growth, survival, and proliferation. Driver mutations provide a selective growth advantage to cells, enabling them to outcompete normal cells and form tumours“, explains MSc Sruthi Hundi, PhD student and co-first author of the study.
Potential model for human breast cancer research
This study underscores the importance of characterizing cancer specimens thoroughly for translational cancer research and emphasizes the need for targeted diagnostic and therapeutic interventions and prognoses based on a deeper understanding of tumour heterogeneity and molecular complexity.
"This study focused on two ductal subtypes of canine mammary tumours with corresponding human breast cancer subtypes. The findings highlight the potential of using canine mammary tumours as a model for studying breast cancer, given the overlap in affected genes and pathways between canine and human tumours," explains Professor Hannes Lohi.
Reference:
Deckwirth V, Hundi S, Hytönen MK, Hannula S, Ellonen P, Björkenheim P,Sukura A, Lohi H. Differential somatic coding variant landscapes between laser microdissected luminal epithelial cells from canine mammary invasive ductal solid carcinoma and comedocarcinoma. BMC Cancer. 2024 Dec 18;24(1):1524. doi: 10.1186/s12885-024-13239-w. PMID: 39696035; PMCID: PMC11657561.