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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 333-349 |
| Number of pages | 17 |
| Journal | Journal of Neuro-Oncology |
| Volume | 94 |
| Issue number | 3 |
| DOIs | |
| State | Published - 2009 |
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Keywords
- Brain tumor
- Canine
- Chromosome
- Comparative genomic hybridization
- Microarray
ASJC Scopus subject areas
- Clinical Neurology
- Cancer Research
- Oncology
- Neurology
Cite this
'Putting our heads together' : Insights into genomic conservation between human and canine intracranial tumors. / Thomas, Rachael; Duke, Shannon E.; Wang, Huixia J.; Breen, Tessa E.; Higgins, Robert; Linder, Keith E.; Ellis, Peter; Langford, Cordelia F.; Dickinson, Peter J; Olby, Natasha J.; Breen, Matthew.
In: Journal of Neuro-Oncology, Vol. 94, No. 3, 2009, p. 333-349.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - 'Putting our heads together'
T2 - Insights into genomic conservation between human and canine intracranial tumors
AU - Thomas, Rachael
AU - Duke, Shannon E.
AU - Wang, Huixia J.
AU - Breen, Tessa E.
AU - Higgins, Robert
AU - Linder, Keith E.
AU - Ellis, Peter
AU - Langford, Cordelia F.
AU - Dickinson, Peter J
AU - Olby, Natasha J.
AU - Breen, Matthew
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
KW - Brain tumor
KW - Canine
KW - Chromosome
KW - Comparative genomic hybridization
KW - Microarray
UR - http://www.scopus.com/inward/record.url?scp=69249248201&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=69249248201&partnerID=8YFLogxK
U2 - 10.1007/s11060-009-9877-5
DO - 10.1007/s11060-009-9877-5
M3 - Article
C2 - 19333554
AN - SCOPUS:69249248201
VL - 94
SP - 333
EP - 349
JO - Journal of Neuro-Oncology
JF - Journal of Neuro-Oncology
SN - 0167-594X
IS - 3
ER -