632: MicroRNAs and Canine Lymphoma

Grant Status: Closed

Grant Amount: $98,766
Dr. William C Kisseberth, DVM PhD, Ohio State University
October 1, 2005 - September 30, 2010
Sponsor(s): Akita Club of America, Inc., American Belgian Malinois Club, American Boxer Charitable Foundation, American Bullmastiff Association, American German Shepherd Dog Charitable Foundation, Inc., Bernese Mountain Dog Club of America, Borzoi Club of America, Chinese Shar-Pei Charitable Trust, Collie Health Foundation, Doberman Pinscher Club of America, Flat-Coated Retriever Foundation, French Bulldog Club of America, Golden Retriever Foundation, Kerry Blue Terrier Foundation, Labrador Retriever Club, Portuguese Water Dog Club of America, Inc., Portuguese Water Dog Foundation, Rhodesian Ridgeback Club of the United States, Rottweiler Health Foundation, San Joaquin Kennel Club, Scottish Terrier Club of America, St. Bernard Club of America, Starlight Fund
Breed(s): -All Dogs
Research Program Area: Treatment

Project Summary

MicroRNAs (miRNAs) are small non-coding RNAs that have been implicated in humans as having a fundamental role in cancer initiation and progression. Canine diffuse large B cell lymphoma (DLBCL) represents one of the most frequently encountered canine neoplasms. We hypothesized that canine DLBCL possess a unique miRNA expression signature and that miRNA dysregulation contributes to chemoresistance and prognosis. In this study we confirmed that miRNAs in the dog are very similar to those in humans, i.e. are highly evolutionarily conserved, and that different miRNA analysis technologies that are applied to human cancers can be similarly applied to canine cancers. Furthermore, miRNA expression in healthy normal tissues is similar in dogs and humans. When we used "next generation" sequencing of canine DLBCL tumor samples to determine their miRNA expression profiles we identified a miRNA that was significantly overexpressed in chemotherapy na�ve tumors compared to chemotherapy relapse tumors from the same patients. Significantly, this was a miRNA with known importance in human cancers. Additionally, we identified a unique miRNA expression signature (multiple coordinately expressed miRNAs) that was associated with overall survival in dogs with DLBCL and treated with a standard chemotherapy regimen. These findings provide insights into mechanisms of lymphomagenesis and potential targets for future therapies.

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