Understanding the driver mutations of canine lymphoma: towards new biomarkers and repositioning human therapies

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Cancer is the number one cause of premature death in dogs and lymphoma is the most common of the canine cancers. Compared to our current knowledge of the genetic changes that occur in human oncogenesis we know little about the mutations that arise in the development of canine cancers including lymphoma. Over the past decade a new generation generation of cancer drugs for treating human cancers have been rationally developed based on the genetic makeup of tumours. An improved understanding of canine lymphoma may allow such "targeted" cancer therapies, originally developed for application to human cancers, to also be "repositioned" for application to veterinary cancers. Using new DNA sequencing technologies, I will search the DNA from canine cancers, beginning with lymphomas, for genetic changes (mutations) that are responsible for converting normal cells to lymphoma cancer cells. Focus will be placed on the genes with shared functions (orthologues) to human lymphoma-related genes. I will also search for dosage changes ("gene expression") likely to be associated with the cancer phenotype. Such analyses can reveal new disease subtypes and prognostic biomarkers that allow us to better predict which animals tumours will respond well to current treatment regimens. Analyzing these types of data requires sophisticated computational approaches collectively referred to as "bioinformatics". New bioinformatics techniques will be developed here to facilitate the analysis of tumour DNA sequence from dogs. I will also develop new molecular approaches to non-invasively search in bodily fluids for the somatic mutations identified in this study. For example, assays will be developed to detect the tumour-specific mutations in the blood plasma of dogs for use as "biomarkers". This work may eventually allow us to diagnose lymphomas more accurately and with less invasive tests than those currently being used. The methods used here can ultimately be generalized to veterinary cancers in both dogs and cats.********