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

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.

Comparative oncology: what dogs and other species can teach us about humans with cancer

“…Meningiomas in both species are highly comparable and share similar phenotypes and gene expression profiles [116,121,123]. Genomic profiling of canine meningiomas for DNA copy number by Thomas et al [11] indicated that canine meningiomas share a limited extent of whole chromosome aneuploidy with their human counterpart. Importantly, the authors hypothesized that by considering the DNA copy number data from both species, the shared aberrations should be the focus of research; for example, in this study they were able to reduce the size of conserved genomic segments by as much as 50-fold.…”

Advances in Diagnostic and Treatment Modalities for Intracranial Tumors

“…As might be expected based on data in humans, there is decreased genomic instability in canine meningiomas compared to generally more aggressive gliomas. Potential similarities to human tumors have been documented including loss of canine chromosome (CFA) 17 and 27 (CFA 17, 27), syntenic to human chromosome (HSA) 1p and 12p; HSA 1, 12 in meningiomas 133, 134…”

Diagnostic Immunohistochemistry of Canine and Feline Intracalvarial Tumors in the Age of Brain Biopsies

“…27 This marker deserves investigation in diagnosis of gliomas in dogs and cats, although these species seem to have their own unique mutational tumor profiles. 129 …”