Soft-tissue sarcomas (STS) are frequent cancers that affect dogs of all breeds and can occur almost anywhere in the body. In humans, STS are classified into more than 100 subtypes using molecular methods, and it is well-established that this classification is essential for accurate diagnosis and treatment. In contrast, classification of canine STS is based on microscopic appearance and lacks markers that are specific for individual subtypes. This leads to diagnostic inconsistency and oversimplification of classification into only few subtypes. As we cannot accurately distinguish between subtypes, canine STS are treated ‚Äòall the same’, while human data shows that subtypes matter very much when it comes to therapy. As a result, up to 30% of canine patients ultimately die from the disease despite receiving surgical treatment. Therapy of canine STS could be greatly improved through a more accurate molecular classification that would inform on patient outcome and identify novel subtype-specific therapeutic options. However, it is currently not possible to develop such a classification, because there is no data that links molecular subtypes to clinical outcome.
Using an innovative approach to analyze specific areas of archival patient samples by laser-capture microdissection (LCM) and RNAsequencing, we are now able to paint a ‚Äòmolecular STS landscape’ that allows identification of subtypes and specific treatments. Leveraging this approach, the overarching goal of this project is to improve diagnosis and therapy for canine STS by understanding which subtypes exist and how they behave clinically. To do this, we will analyze 160 STS samples for which we have very detailed clinical data and combine these data with our existing ‚ÄòSTS landscape’ that consists of data from 106 tumors and is currently being expanded to 196 cases. By creating a detailed molecular ‚ÄòSTS landscape’ of a total of 356 STS cases, this project will allow identification of molecular subtypes, their association with outcome, and pinpoint subtype-specific therapies to improve clinical care for these underserved patients. Finally, as canine ST are considered good models to better understand HS in humans, these results also have the potential to significantly impact human health from a one-health perspective.