Common Molecular Alterations in Canine Oligodendroglioma and Human Malignant Gliomas and Potential Novel Therapeutic Targets
Spontaneous canine (Canis lupus) oligodendroglioma (ODG) holds tremendous potential as an immunocompetent large animal model of human malignant gliomas (MG). However, the feasibility of utilizing this model in pre-clinical studies depends on a thorough understanding of the similarities and differenc...
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ftiupui:oai:scholarworks.indianapolis.iu.edu:1805/21197 2024-09-15T18:01:28+00:00 Common Molecular Alterations in Canine Oligodendroglioma and Human Malignant Gliomas and Potential Novel Therapeutic Targets Mitchell, Dana Chintala, Sreenivasulu Fetcko, Kaleigh Henriquez, Mario Tewari, Brij N. Ahmed, Atique Bentley, R. Timothy Dey, Mahua Neurological Surgery, School of Medicine 2019-08-14 application/pdf https://hdl.handle.net/1805/21197 en_US eng Frontiers 10.3389/fonc.2019.00780 Frontiers in Oncology Mitchell, D., Chintala, S., Fetcko, K., Henriquez, M., Tewari, B. N., Ahmed, A., … Dey, M. (2019). Common Molecular Alterations in Canine Oligodendroglioma and Human Malignant Gliomas and Potential Novel Therapeutic Targets. Frontiers in oncology, 9, 780. doi:10.3389/fonc.2019.00780 https://hdl.handle.net/1805/21197 http://creativecommons.org/licenses/by/3.0/us/ PMC Canine glioma Glioblastoma Molecular therapeutic targets Malignant glioma Anaplastic oligodendroglioma Article 2019 ftiupui https://doi.org/10.3389/fonc.2019.00780 2024-08-08T03:18:34Z Spontaneous canine (Canis lupus) oligodendroglioma (ODG) holds tremendous potential as an immunocompetent large animal model of human malignant gliomas (MG). However, the feasibility of utilizing this model in pre-clinical studies depends on a thorough understanding of the similarities and differences of the molecular pathways associated with gliomas between the two species. We have previously shown that canine ODG has an immune landscape and expression pattern of commonly described oncogenes similar to that of human MG. In the current study, we performed a comprehensive analysis of canine ODG RNAseq data from 4 dogs with ODG and 2 normal controls to identify highly dysregulated genes in canine tumors. We then evaluated the expression of these genes in human MG using Xena Browser, a publicly available database. STRING-database inquiry was used in order to determine the suggested protein associations of these differentially expressed genes as well as the dysregulated pathways commonly enriched by the protein products of these genes in both canine ODG and human MG. Our results revealed that 3,712 (23%) of the 15,895 differentially expressed genes demonstrated significant up- or downregulation (log2-fold change > 2.0). Of the 3,712 altered genes, ~50% were upregulated (n = 1858) and ~50% were downregulated (n = 1854). Most of these genes were also found to have altered expression in human MG. Protein association and pathway analysis revealed common pathways enriched by members of the up- and downregulated gene categories in both species. In summary, we demonstrate that a similar pattern of gene dysregulation characterizes both human MG and canine ODG and provide additional support for the use of the canine model in order to therapeutically target these common genes. The results of such therapeutic targeting in the canine model can serve to more accurately predict the efficacy of anti-glioma therapies in human patients. Article in Journal/Newspaper Canis lupus Indiana University - Purdue University Indianapolis: IUPUI Scholar Works Frontiers in Oncology 9 |
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Open Polar |
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Indiana University - Purdue University Indianapolis: IUPUI Scholar Works |
op_collection_id |
ftiupui |
language |
English |
topic |
Canine glioma Glioblastoma Molecular therapeutic targets Malignant glioma Anaplastic oligodendroglioma |
spellingShingle |
Canine glioma Glioblastoma Molecular therapeutic targets Malignant glioma Anaplastic oligodendroglioma Mitchell, Dana Chintala, Sreenivasulu Fetcko, Kaleigh Henriquez, Mario Tewari, Brij N. Ahmed, Atique Bentley, R. Timothy Dey, Mahua Common Molecular Alterations in Canine Oligodendroglioma and Human Malignant Gliomas and Potential Novel Therapeutic Targets |
topic_facet |
Canine glioma Glioblastoma Molecular therapeutic targets Malignant glioma Anaplastic oligodendroglioma |
description |
Spontaneous canine (Canis lupus) oligodendroglioma (ODG) holds tremendous potential as an immunocompetent large animal model of human malignant gliomas (MG). However, the feasibility of utilizing this model in pre-clinical studies depends on a thorough understanding of the similarities and differences of the molecular pathways associated with gliomas between the two species. We have previously shown that canine ODG has an immune landscape and expression pattern of commonly described oncogenes similar to that of human MG. In the current study, we performed a comprehensive analysis of canine ODG RNAseq data from 4 dogs with ODG and 2 normal controls to identify highly dysregulated genes in canine tumors. We then evaluated the expression of these genes in human MG using Xena Browser, a publicly available database. STRING-database inquiry was used in order to determine the suggested protein associations of these differentially expressed genes as well as the dysregulated pathways commonly enriched by the protein products of these genes in both canine ODG and human MG. Our results revealed that 3,712 (23%) of the 15,895 differentially expressed genes demonstrated significant up- or downregulation (log2-fold change > 2.0). Of the 3,712 altered genes, ~50% were upregulated (n = 1858) and ~50% were downregulated (n = 1854). Most of these genes were also found to have altered expression in human MG. Protein association and pathway analysis revealed common pathways enriched by members of the up- and downregulated gene categories in both species. In summary, we demonstrate that a similar pattern of gene dysregulation characterizes both human MG and canine ODG and provide additional support for the use of the canine model in order to therapeutically target these common genes. The results of such therapeutic targeting in the canine model can serve to more accurately predict the efficacy of anti-glioma therapies in human patients. |
author2 |
Neurological Surgery, School of Medicine |
format |
Article in Journal/Newspaper |
author |
Mitchell, Dana Chintala, Sreenivasulu Fetcko, Kaleigh Henriquez, Mario Tewari, Brij N. Ahmed, Atique Bentley, R. Timothy Dey, Mahua |
author_facet |
Mitchell, Dana Chintala, Sreenivasulu Fetcko, Kaleigh Henriquez, Mario Tewari, Brij N. Ahmed, Atique Bentley, R. Timothy Dey, Mahua |
author_sort |
Mitchell, Dana |
title |
Common Molecular Alterations in Canine Oligodendroglioma and Human Malignant Gliomas and Potential Novel Therapeutic Targets |
title_short |
Common Molecular Alterations in Canine Oligodendroglioma and Human Malignant Gliomas and Potential Novel Therapeutic Targets |
title_full |
Common Molecular Alterations in Canine Oligodendroglioma and Human Malignant Gliomas and Potential Novel Therapeutic Targets |
title_fullStr |
Common Molecular Alterations in Canine Oligodendroglioma and Human Malignant Gliomas and Potential Novel Therapeutic Targets |
title_full_unstemmed |
Common Molecular Alterations in Canine Oligodendroglioma and Human Malignant Gliomas and Potential Novel Therapeutic Targets |
title_sort |
common molecular alterations in canine oligodendroglioma and human malignant gliomas and potential novel therapeutic targets |
publisher |
Frontiers |
publishDate |
2019 |
url |
https://hdl.handle.net/1805/21197 |
genre |
Canis lupus |
genre_facet |
Canis lupus |
op_source |
PMC |
op_relation |
10.3389/fonc.2019.00780 Frontiers in Oncology Mitchell, D., Chintala, S., Fetcko, K., Henriquez, M., Tewari, B. N., Ahmed, A., … Dey, M. (2019). Common Molecular Alterations in Canine Oligodendroglioma and Human Malignant Gliomas and Potential Novel Therapeutic Targets. Frontiers in oncology, 9, 780. doi:10.3389/fonc.2019.00780 https://hdl.handle.net/1805/21197 |
op_rights |
http://creativecommons.org/licenses/by/3.0/us/ |
op_doi |
https://doi.org/10.3389/fonc.2019.00780 |
container_title |
Frontiers in Oncology |
container_volume |
9 |
_version_ |
1810438609788993536 |