2214: Identification of a 5-10Mb BAC Set as a Cytogenetic Resource and for the Development of an Ordered CGH Microarray for Cancer Studies in the Dog

Grant Status: Closed

Grant Amount: $18,652.5
Matthew Breen, PhD; Animal Health Trust
July 16, 2001 - September 30, 2003

Sponsor(s):

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

The study of aberrant chromosome structure has significantly increased our understanding of the cause and progression of human cancers. Many cancers are common to both dogs and humans, in part reflecting the high degree of similarity in their genetic material and in their environmental exposure to carcinogens. The extent and identity of chromosome aberrations associated with canine cancers, however, remains largely unknown. This is primarily due to the difficulty in identifying dog chromosomes by conventional means alone. Comparative genomic hybridization (CGH) is a technique that allows a comprehensive analysis of chromosome aberrations present within tumors. We have developed this technique for application to dog cancers and are obtaining valuable information. However, chromosome-based CGH is labor intensive, has a limited resolution and requires detailed knowledge of dog chromosomes. In this study we aim to identify set of large insert clones that are evenly spaced, at small intervals, along all dog chromosomes. These clones will be a very valuable resource for chromosome studies of dog cancers. The clones will be used to generate an ordered microarray to replace chromosome-based analyses. This will significantly and rapidly advance the study of canine cancer, leading to improved diagnosis and prognosis and thus health and welfare.

Publication(s)

Breen, M., Hitte, C., Lorentzen, T. D., Thomas, R., Cadieu, E., Sabacan, L., … Ostrander, E. A. (2004). An integrated 4249 marker FISH/RH map of the canine genome. BMC Genomics, 5(65), 11.
 
Fosmire, S. P., Thomas, R., Jubala, C. M., Wojcieszyn, J. W., Valli, V. E. O., Getzy, D. M., … Modiano, J. F. (2007). Inactivation of the p16 Cyclin-Dependent Kinase Inhibitor in High-Grade Canine Non-Hodgkin’s T-Cell Lymphoma. Veterinary Pathology, 44(4), 467–478. https://doi.org/10.1354/vp.44-4-467
 
Modiano, J. F., Breen, M., Burnett, R. C., Parker, H. G., Inusah, S., Thomas, R., … Avery, A. C. (2005). Distinct B-Cell and T-Cell Lymphoproliferative Disease Prevalence among Dog Breeds Indicates Heritable Risk. Cancer Research, 65(13), 5654–5661. https://doi.org/10.1158/0008-5472.CAN-04-4613
 
Rebbeck, C. A., Thomas, R., Breen, M., Leroi, A. M., & Burt, A. (2009). ORIGINS AND EVOLUTION OF A TRANSMISSIBLE CANCER. Evolution, 63(9), 2340–2349. https://doi.org/10.1111/j.1558-5646.2009.00724.x
 
Thomas, R. (2005). Construction of a 2-Mb resolution BAC microarray for CGH analysis of canine tumors. Genome Research, 15(12), 1831–1837. https://doi.org/10.1101/gr.3825705
 
Thomas, R., Bridge, W., Benke, K., & Breen, M. (2003). Isolation and chromosomal assignment of canine genomic BAC clones representing 25 cancer-related genes. Cytogenetic and Genome Research, 102(1–4), 249–253. https://doi.org/10.1159/000075757
 
Thomas, R., Fiegler, H., Ostrander, E. A., Galibert, F., Carter, N. P., & Breen, M. (2003). A canine cancer-gene microarray for CGH analysis of tumors. Cytogenetic and Genome Research, 102(1–4), 254–260. https://doi.org/10.1159/000075758
 
Thomas, R, Smith, K. C., Ostrander, E. A., Galibert, F., & Breen, M. (2003). Chromosome aberrations in canine multicentric lymphomas detected with comparative genomic hybridisation and a panel of single locus probes. British Journal of Cancer, 89(8), 1530–1537. https://doi.org/10.1038/sj.bjc.6601275
 
Thomas, Rachael, Duke, S. E., Bloom, S. K., Breen, T. E., Young, A. C., Feiste, E., … Breen, M. (2007). A Cytogenetically Characterized, Genome-Anchored 10-Mb BAC Set and CGH Array for the Domestic Dog. Journal of Heredity, 98(5), 474–484. https://doi.org/10.1093/jhered/esm053
 
Thomas, Rachael, Rebbeck, C., Leroi, A. M., Burt, A., & Breen, M. (2009). Extensive conservation of genomic imbalances in canine transmissible venereal tumors (CTVT) detected by microarray-based CGH analysis. Chromosome Research, 17(7), 927–934. https://doi.org/10.1007/s10577-009-9080-8
 
Tsai, P.-C., & Breen, M. (2012). Array-based comparative genomic hybridization–guided identification of reference genes for normalization of real-time quantitative polymerase chain reaction assay data for lymphomas, histiocytic sarcomas, and osteosarcomas of dogs. American Journal of Veterinary Research, 73(9), 1335–1343. https://doi.org/10.2460/ajvr.73.9.1335

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