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| Status |
Public on Sep 26, 2013 |
| Title |
Comparative Transcriptional Analysis of Canine and Human Diffuse Large B cell Lymphoma (DLBCL). Molecular Signatures of NF-κB Pathway Activation and Sub-Classification of Canine DLBCL. |
| Organism |
Canis lupus familiaris |
| Experiment type |
Expression profiling by array
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| Summary |
In this study, we present the first comparison of global transcriptional changes taking place in canine lymphoma and human diffuse large B-cell lymphoma (DLBCL), with particular reference to the nuclear factor-kappaB (NF-κB) pathway. Microarray data generated from lymph nodes diagnosed with canine DLBCL and healthy lymph nodes were used for differential expression analysis, co-expression analysis and pathway analysis, and compared with analysis of publicly available microarray data from human healthy and DLBCL lymph nodes. The comparisons between species at gene level were performed by mapping the probesets in canine microarrays to orthologous genes in humans and vice versa.
A considerable number of differentially expressed genes between canine lymphoma and healthy lymph node samples were also found differentially expressed between human DLBCL and healthy lymph node samples. Principal component analysis (PCA) using a literature derived 120 NF-κB target gene set mapped to 199 orthologous canine array probesets and 259 human array probesets clearly separated the healthy and cancer samples in both canine and human datasets.
The analysis demonstrated that for both human and canine DLBCL there is activation of the NF-κB/p65 canonical pathway rather than the alternative pathway. This has therapeutic implications for the use of specific pathway inhibitors for the treatment of DLBCL for both species and also indicates that naturally occurring canine lymphoma could be used as a model to study therapeutic strategies for human lymphoma. The model was further validated by the identification of molecular signatures that could sub-classify canine DLBCL into activated B-cell-like (ABC) or germinal centre B-cell-like (GCB) types equivalent to human subtypes.
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| Overall design |
Canine DLBCL patients were recruited via the clinical oncology service of the University of Edinburgh Royal (Dick) School of Veterinary Studies (DJA), and the University of Wisconsin-Madison School of Veterinary Medicine (DMV). Lymph node biopsy samples were taken, as part of normal diagnostic procedures, from dogs newly diagnosed with lymphoma (naïve) and samples from dogs that had relapsed following standard of care CHOP chemotherapy. Only dogs with confirmed DLBCL after pathological grading were used in this study. This included standard histopathological grading by two independent pathologists and CD3/PAX5 marker analysis. Normal lymph node samples were obtained from canines that were euthanized for non-lymphoma conditions. Microarray data were generated from 35 canine samples (25 DLBCL and 10 healthy) in total. However, data from 2 canine DLBCL samples did not meet our required quality and were removed from further analysis. Only data from 33 (23 DLBCL and 10 healthy) samples were used for analysis. The generated data were used for differential expression analysis, co-expression analysis and pathway analysis, and compared with analysis of publicly available microarray data (GSE12195) from human healthy and DLBCL lymph nodes. The comparisons between species at gene level were performed by mapping the probesets in canine microarrays to orthologous genes in humans and vice versa.
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| Contributor(s) |
Mudaliar MA, Haggart RD, Miele G, Sellar G, Tan KA, Goodlad J, Milne E, Vail DM, Kurzman ID, Crowther DJ, Argyle DJ |
| Citation(s) |
24023754 |
| Submission date |
Jul 22, 2011 |
| Last update date |
Sep 27, 2013 |
| Contact name |
Manikhandan A V Mudaliar |
| E-mail(s) |
innovatebio@gmail.com
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| Organization name |
University of Glasgow
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| Department |
College of Medical, Veterinary and Life Sciences
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| Lab |
Institute of Infection, Immunity and Inflammation
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| Street address |
Room B528, Sir Graeme Davies Building, 120 University Place
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| City |
Glasgow |
| State/province |
Scotland |
| ZIP/Postal code |
G12 8TA |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL3738 |
[Canine_2] Affymetrix Canine Genome 2.0 Array |
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| Samples (33)
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| Relations |
| BioProject |
PRJNA144259 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE30881_RAW.tar |
127.3 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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