Abstract
Canine transmissible venereal tumor (CTVT) is an intriguing cancer that is transmitted naturally as an allograft by transplantation of viable tumor cells from affected to susceptible dogs. At least initially, the tumor is able to evade the host's immune response; thus, CTVT has potential to provide novel insights into tumor immunobiology. The nature of CTVT as a “contagious” cancer, originating from a common ancestral source of infection, has been demonstrated previously by a series of studies comparing geographically distinct tumors at the molecular level. While these studies have revealed that apparently unrelated tumors share a striking degree of karyotypic conservation, technological restraints have limited the ability to investigate the chromosome composition of CTVTs in any detail. We present characterization of a strategically selected panel of CTVT cases using microarray-based comparative genomic hybridization analysis at ~one-megabase resolution. These data show for the first time that the tumor presents with an extensive range of non-random chromosome copy number aberrations that are distributed widely throughout the dog genome. The majority of abnormalities detected were imbalances of small subchromosomal regions, often involving centromeric and telomeric sequences. All cases also showed the sex chromosome complement XO. There was remarkable conservation in the cytogenetic profiles of the tumors analyzed, with only minor variation observed between different cases. These data suggest that the CTVT genome demonstrates a vast degree of both structural and numerical reorganization that is maintained during transmission among the domestic dog population.
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Abbreviations
- aCGH:
-
array-based comparative genomic hybridization
- BAC:
-
bacterial artificial chromosome
- CFA:
-
Canis familiaris
- CGH:
-
comparative genomic hybridization
- CHORI:
-
Children's Hospital Oakland Research Institute
- CNA:
-
copy number aberration
- CTVT:
-
canine transmissible venereal tumor
- DAPI:
-
4′,6-diamidino-2-phenylindole
- DFTD:
-
devil facial tumor disease
- FISH:
-
fluorescence in situ hybridization
- LINE-1:
-
long interspersed nuclear element
- Mb:
-
megabase
- RPCI:
-
Roswell Park Cancer Institute
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Acknowledgements
We thank the following for contributing the CTVT specimens used in this study: Ayoub Banderker, Antonio Ortrga-Pacheco, Jean Gilchrist, and Belinda Rivera. Canine cancer genetics work at NCSU is supported by funding from the American Kennel Club Canine Health Foundation and the Morris Animal Foundation. This work was also supported by the National Environmental Research Council (NERC) and the Breakthrough Breast Cancer Research Centre, part of the Institute of Cancer Research (ICR).
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Thomas, R., Rebbeck, C., Leroi, A.M. et al. Extensive conservation of genomic imbalances in canine transmissible venereal tumors (CTVT) detected by microarray-based CGH analysis. Chromosome Res 17, 927–934 (2009). https://doi.org/10.1007/s10577-009-9080-8
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DOI: https://doi.org/10.1007/s10577-009-9080-8