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‘Putting our heads together’: insights into genomic conservation between human and canine intracranial tumors

  • Laboratory Investigation - Human/animal tissue
  • Published:
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Abstract

Numerous attributes render the domestic dog a highly pertinent model for cancer-associated gene discovery. We performed microarray-based comparative genomic hybridization analysis of 60 spontaneous canine intracranial tumors to examine the degree to which dog and human patients exhibit aberrations of ancestrally related chromosome regions, consistent with a shared pathogenesis. Canine gliomas and meningiomas both demonstrated chromosome copy number aberrations (CNAs) that share evolutionarily conserved synteny with those previously reported in their human counterpart. Interestingly, however, genomic imbalances orthologous to some of the hallmark aberrations of human intracranial tumors, including chromosome 22/NF2 deletions in meningiomas and chromosome 1p/19q deletions in oligodendrogliomas, were not major events in the dog. Furthermore, and perhaps most significantly, we identified highly recurrent CNAs in canine intracranial tumors for which the human orthologue has been reported previously at low frequency but which have not, thus far, been associated intimately with the pathogenesis of the tumor. The presence of orthologous CNAs in canine and human intracranial cancers is strongly suggestive of their biological significance in tumor development and/or progression. Moreover, the limited genetic heterogenity within purebred dog populations, coupled with the contrasting organization of the dog and human karyotypes, offers tremendous opportunities for refining evolutionarily conserved regions of tumor-associated genomic imbalance that may harbor novel candidate genes involved in their pathogenesis. A comparative approach to the study of canine and human intracranial tumors may therefore provide new insights into their genetic etiology, towards development of more sophisticated molecular subclassification and tailored therapies in both species.

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Acknowledgements

We would like to acknowledge Pragna Mehta and the Veterinary Neurology and Pathology residents and clinicians from North Carolina State University and the University of California at Davis for assistance with tissue procurement. We thank Eric Seiser for assistance with data analysis. This work was supported by grants from the National Institutes of Health (NS051190) and the American Kennel Club Canine Health Foundation (CHF-403) awarded to MB and NJO. CFL and PE are supported by funds from the Wellcome Trust. HJW is supported by National Science Foundation Award (DMS-0706963). PD and RJH are supported by the Paul C and Borghild T Petersen Foundation.

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Authors and Affiliations

  1. Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, NC, 27606, USA

    Rachael Thomas, Shannon E. Duke & Matthew Breen

  2. Center for Comparative Medicine and Translational Research, North Carolina State University, Raleigh, NC, 27606, USA

    Rachael Thomas, Keith E. Linder, Natasha J. Olby & Matthew Breen

  3. Department of Statistics, College of Agriculture and Life Sciences, North Carolina State University, Patterson Hall, 2501 Founders Drive, Raleigh, NC, 27695, USA

    Huixia J. Wang

  4. Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, NC, 27606, USA

    Tessa E. Breen & Natasha J. Olby

  5. Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California-Davis, Davis, CA, 95616, USA

    Robert J. Higgins

  6. Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA

    Keith E. Linder

  7. Microarray Facility, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK

    Peter Ellis & Cordelia F. Langford

  8. Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA, 95616, USA

    Peter J. Dickinson

  9. Cancer Genetics Program, UNC Lineberger Comprehensive Cancer Center, Chapel Hill, NC, 27599, USA

    Matthew Breen

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  1. Rachael Thomas
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Correspondence to Matthew Breen.

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Thomas, R., Duke, S.E., Wang, H.J. et al. ‘Putting our heads together’: insights into genomic conservation between human and canine intracranial tumors. J Neurooncol 94, 333–349 (2009). https://doi.org/10.1007/s11060-009-9877-5

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  • DOI: https://doi.org/10.1007/s11060-009-9877-5

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