2667: Cellular Genomics - Molecular Cytogenetic Investigation of Canine Soft Tissue Sarcomas

Grant Status: Closed

Grant Amount: $99,504
Matthew Breen, PhD; North Carolina State University
April 1, 2004 - March 31, 2006
Sponsor(s): Newfoundland Club of America Charitable Trust, Rottweiler Health Foundation
Breed(s): Bernese Mountain Dog, Flat-Coated Retriever, Boxer, Golden Retriever
Research Program Area: Oncology

Abstract

It has been established that non-random chromosome aberrations are characteristic of specific types of many different human cancers. The knowledge of such aberrations has identified areas of the human genome to be targeted for further research. In the dog the extent and identity of chromosome aberrations associated with specific cancers is still largely unknown. In certain breeds, such as the Flat-Coated Retriever and Bernese Mountain Dog, soft tissue sarcomas account for up to 50 percent of all malignant tumors and thus represent a serious health and welfare issue for those breeds. These tumors are difficult to classify by conventional means and so attention is required to develop alternative approaches. Human soft tissue sarcomas have been demonstrated to be associated with specific chromosomal aberrations that have been shown to have both diagnostic and prognostic significance. This proposal will make use of major recent advances in canine molecular cytogenetics to identify recurrent chromosome aberrations associated with canine soft tissue sarcomas, in particular those of histiocytic origin. This project will identify areas of the canine genome associated with such cancers for further investigation at the sub-chromosomal level.

Publication(s)

Breen, M. (2008). Canine cytogenetics - from band to basepair. Cytogenetic and Genome Research, 120(1–2), 50–60. https://doi.org/10.1159/000118740

Fosmire, S. P., Dickerson, E. B., Scott, A. M., Bianco, S. R., Pettengill, M. J., Meylemans, H., … Modiano, J. F. (2004). Canine malignant hemangiosarcoma as a model of primitive angiogenic endothelium. Laboratory Investigation, 84(5), 562–572. https://doi.org/10.1038/labinvest.3700080

Hedan, B., Thomas, R., Motsinger-Reif, A., Abadie, J., Andre, C., Cullen, J., & Breen, M. (2011). Molecular cytogenetic characterization of canine histiocytic sarcoma: A spontaneous model for human histiocytic cancer identifies deletion of tumor suppressor genes and highlights influence of genetic background on tumor behavior. BMC Cancer, 11(1). https://doi.org/10.1186/1471-2407-11-201

Kennerly, E., Thomson, S., Olby, N., Breen, M., & Gibson, G. (2004). Comparison of regional gene expression differences in the brains of the domestic dog and human. Human Genomics, 1(6), 435. https://doi.org/10.1186/1479-7364-1-6-435

Modiano, J F, Breen, M., Valli, V. E. O., Wojcieszyn, J. W., & Cutter, G. R. (2007). Predictive value of p16 or Rb inactivation in a model of naturally occurring canine non-Hodgkin’s lymphoma. Leukemia, 21(1), 184–187. https://doi.org/10.1038/sj.leu.2404392

Modiano, Jaime F, Breen, M., Lana, S. E., Ehrhart, N., Fosmire, S. P., Thomas, R., … Bellgrau, D. (2006). Naturally occurring translational models for development of cancer gene therapy. Gene Therapy and Molecular Biology, 10, 31–40.

Philipp, U., Quignon, P., Scott, A., Rak, S., André, C., Breen, M., & Leeb, T. (2003). Assignment of the canine myosin Va gene (MYO5A) to chromosome 30q14 by fluorescence in situ hybridization and radiation hybrid mapping. Cytogenetic and Genome Research, 101(1), 92C-92C. https://doi.org/10.1159/000073681

Philipp, U., Scott, A., Quignon, P., André, C., Breen, M., & Leeb, T. (2003). Assignment of the RAB27A gene to canine chromosome 30q15.1 by fluorescence in situ hybridization and radiation hybrid mapping. Cytogenetic and Genome Research, 101(1), 92E. https://doi.org/10.1159/000073683

Rak, S. G., Drogemuller, C., Leeb, T., Quignon, P., Andre, C., & Scott, A. (2003). Chromosomal assignment of 20 candidate genes for canine congenital sensorineural deafness by FISH and RH mapping. Cytogenetic and Genome Research, 101(2), 130–135.

Tiret, L., Blot, S., Kessler, J.-L., Gaillot, H., Breen, M., & Panthier, J.-J. (2003). The cnm locus, a canine homologue of human autosomal forms of centronuclear myopathy, maps to chromosome2. Human Genetics, 113(4), 297–306. https://doi.org/10.1007/s00439-003-0984-7

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