02772: Identifying Early Stage Ultra-rare Mutations as Predictive Biomarkers of Lymphoma in High-risk versus Low-risk Breeds Within the Dog Aging Project

Grant Status: Open

Grant Amount: $75,600
Daniel Promislow, PhD; University of Washington
March 1, 2020 - February 28, 2021

Sponsor(s): Bouvier Health Foundation, Flat-Coated Retriever Foundation

Breed(s): -All Dogs
Research Program Area: Oncology - Lymphoma
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Abstract

The most common type of cancer in dogs is lymphoma, with ~80,000 cases diagnosed annually in the United States. Breeds vary in their risk of lymphoma, but it is unclear why there is variation despite considerable effort to identify the genetics of cancer risk and progression in dogs. Cancer typically arises from the accumulation of non-inherited (i.e. somatic) mutations. However, variation among breeds in cancer risk could be due to breed-specific variation in the types of mutations, the rate of accumulation of mutations, or the downstream effects of mutations in healthy dogs. This study will use novel sequencing technology to test the hypothesis that breed-specific lymphoma risk is due to variation in the frequency and type of rare precancerous mutations. Normally, measuring these low-frequency mutations has been beyond the range of standard sequencing technology, which is limited to detecting mutations present in >1% of cells. The new technology applied here represents a >10,000-fold improvement in accuracy, enabling the investigators to accurately detect a precancerous mutation present at a single site at a frequency of just one out of every 10 million DNA base pairs. By determining if mutation frequency in blood of healthy high-risk and low-risk dogs can predict lymphoma risk, this work could lead to the development of novel tests for the early diagnosis and prognosis of canine lymphoma. This work has the potential to shed light on the mechanisms that underlie breed-specific variation in lymphoma risk, and in the long term, could lead to the development of novel tests for the early diagnosis and prognosis of canine lymphoma.

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