01660: Identifying the Genes That Confer Risk for Osteosarcoma

Grant Status: Open

Grant Amount: $120,000
Carlos E. Alvarez, PhD; The Research Institute at Nationwide Children's Hospital
January 1, 2012 - December 31, 2019

Sponsor(s): Afghan Hound Club of America, Inc., American Bullmastiff Association, German Shepherd Dog Club of America, Great Pyrenees Club of America, Saluki Health Research, Inc.

Breed(s): Rottweiler, Greyhound, Golden Retriever
Research Program Area: Oncology - Osteosarcoma
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Abstract

Osteosarcoma (OSA) is the most common cancer of the bone in both dogs and humans. A prime candidate for investigation of the genetic component of OSA is the Greyhound, which has the highest risk of OSA of any breed. However, despite significant effort, classical genetic approaches have not identified any Greyhound variant that accounts for most OSA cases in that breed. Dr. Alvarez proposes that Greyhound OSA variants have been directly or indirectly selected for in racing performance, consistent with the vastly elevated incidence in racing vs. show Greyhounds. If this is true and all racers carried an OSA mutation on both chromosomes, then this could not be detected using classical approaches (which require different genetic markers to distinguish cases v. controls). Here Dr. Alvarez proposes an innovative genetic approach that is impervious to the limitations described above, and enables genome-wide discovery of Greyhound variation with large effects on OSA risk. Such findings would lead to rapid development of therapies and clinical trials in dogs, and translation to human medicine.

Publication(s)

Alvarez, C. E. (2014). Naturally Occurring Cancers in Dogs: Insights for Translational Genetics and Medicine. ILAR Journal, 55(1), 16–45. https://doi.org/10.1093/ilar/ilu010

Clemente-Vicario, F., Alvarez, C. E., Rowell, J. L., Roy, S., London, C. A., Kisseberth, W. C., & Lorch, G. (2015). Human Genetic Relevance and Potent Antitumor Activity of Heat Shock Protein 90 Inhibition in Canine Lung Adenocarcinoma Cell Lines. PLOS ONE, 10(11), e0142007. https://doi.org/10.1371/journal.pone.0142007

Lutful Kabir, F. M., Alvarez, C. E., & Bird, R. C. (2015). Canine Mammary Carcinomas: A Comparative Analysis of Altered Gene Expression. Veterinary Sciences, 3(1). https://doi.org/10.3390/vetsci3010001

Zaldívar-López, S., Rowell, J. L., Fiala, E. M., Zapata, I., Couto, C. G., & Alvarez, C. E. (2017). Comparative genomics of canine hemoglobin genes reveals primacy of beta subunit delta in adult carnivores. BMC Genomics, 18(1). https://doi.org/10.1186/s12864-017-3513-0

Zapata, I., Moraes, L. E., Fiala, E. M., Zaldivar-Lopez, S., Couto, C. G., Rowell, J. L., & Alvarez, C. E. (2019). Risk-modeling of dog osteosarcoma genome scans shows individuals with Mendelian-level polygenic risk are common. BMC Genomics, 20(1), 226. https://doi.org/10.1186/s12864-019-5531-6

Zapata, I., Serpell, J. A., & Alvarez, C. E. (2016). Genetic mapping of canine fear and aggression. BMC Genomics, 17(1). https://doi.org/10.1186/s12864-016-2936-3

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