00615B: Heritable and Sporadic Genetic Lesions in Canine Lymphoma

Grant Status: Closed

Grant Amount: $149,369
Dr. Matthew Breen, PhD, North Carolina State University
August 1, 2008 - July 31, 2011
Sponsor(s): Akita Club of America, Inc., American Bloodhound Club, American Bouvier des Flandres Club - Bouvier Health Foundation, American Boxer Charitable Foundation, American Bullmastiff Association, American Cavalier King Charles Spaniel Club Charitable Trust, American German Shepherd Dog Charitable Foundation, Inc., American Shih Tzu Club, Inc., Atlantic States Briard Club, Inc., Australian Shepherd Health & Genetics Institute, Bernese Mountain Dog Club of America, Briard Club of America Health & Education Trust, Chinese Shar-Pei Charitable Trust, Collie Health Foundation, Doberman Pinscher Club of America, Estate of Virginia Lyn Tarquinio, Flat-Coated Retriever Foundation, French Bulldog Club of America, German Shepherd Dog Club of America, German Wirehaired Pointer Club of America, Golden Retriever Foundation, Jeffrey Pepper, Labrador Retriever Club, Orthopedic Foundation for Animals, Portuguese Water Dog Club of America, Inc., Rhodesian Ridgeback Club of the United States, Rottweiler Health Foundation, Samoyed Club of America Education & Research Foundation, San Joaquin Kennel Club, Scottish Terrier Club of America, St. Bernard Club of America, Starlight Fund, United States Australian Shepherd Association, United States Australian Shepherd Foundation, Vizsla Club of America Welfare Foundation
Breed(s): -All Dogs
Research Program Area: Prevention

Project Summary

The overall goal of this study was to use molecular cytogenetics to evaluate recurrent DNA copy number changes in canine lymphoma. Initially we aimed to evaluate 100 cases, but by merging data with a parallel study we were able to generate data from over 250 cases. This resulted in a substantial volume of data that allowed us to determine which regions of the canine genome are subject to copy number changes in lymphoma subtypes. A subset of 150 cases of lymphoma, available as fresh lymph node biopsies, was used initially to provide optimum quality cytogenetic data. These data revealed that in canine B cell lymphoma, the number of DNA copy number aberrations is far fewer than has been reported in human B cell lymphoma, while the extent of aberration in canine and human T cell lymphoma was comparable. The clinical and pathological presentation of lymphoma in both dog and human are highly comparable. In consideration of these data, we concluded that while human lymphoma presents with a large number of DNA copy number aberrations, our canine data suggest that many of these aberrations are likely consequential changes, the key changes being those few that are shared between human and dog. While fresh tissue specimens are ideal for cytogenetic analysis, we also have developed a means to obtain data from archival specimens, represented by tumor samples that have been fixed in formalin and stored in paraffin blocks. These are the specimens that are evaluated by a pathologist during diagnosis. A major advantage to the use of archival samples is that we can select cases associated with detailed clinical and pathological information from the outset. In this study we analyzed cytogenetic data from 102 archival cases of canine lymphoma and demonstrated that the distribution of DNA copy numbers was comparable to that we had identified in 150 cases of fresh tissue. These data suggest that we are able to make use of large pathology archives as a source of case material for cytogenetic analysis. In this particular project the net results were that we were able to assess DNA copy number changes in all 252 cases and add substantially to the overall cohort. With this large data set we identified several high frequency DNA copy number aberrations, some of which are associated recurrently with either B cell or T cell phenotype and some of which may be associated with further subtypes. In addition many of the cases used in this study were treated with standard of care chemotherapy and so as we follow the outcome of these patients we will be in a position to determine if any of the recurrent chromosome changes we have identified are associated with prognosis. As we proceed we now are using much higher resolution technology, allowing us to narrow down the regions of interest and ultimately lead us to more accurate gene discovery.

Publication(s)

- Thomas, R., E. L. Seiser, A. A. Motsinger-Reif, L. Borst, V. E. Valli, K. Kelley, S. E. Suter, D. Argyle, K. Burgess, J. Bell, K. Lindblad-Toh, J. F. Modiano and M. Breen (2011). "Refining tumor-associated aneuploidy through 'genomic recoding' of recurr

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