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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doaj-e9e6773938c0429d8183b6fcc0fb29712020-11-25T01:07:41ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2019-08-01910.3389/fonc.2019.00780474947Common Molecular Alterations in Canine Oligodendroglioma and Human Malignant Gliomas and Potential Novel Therapeutic TargetsDana Mitchell0Sreenivasulu Chintala1Kaleigh Fetcko2Mario Henriquez3Brij N. Tewari4Atique Ahmed5R. Timothy Bentley6Mahua Dey7Department of Neurosurgery, Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN, United StatesDepartment of Neurosurgery, Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN, United StatesDepartment of Neurosurgery, Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN, United StatesDepartment of Neurosurgery, Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN, United StatesDepartment of Neurosurgery, Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN, United StatesDepartment of Neurological Surgery, Northwestern University, Chicago, IL, United StatesDepartment of Veterinary Clinical Sciences, Purdue University Center for Cancer Research, Purdue University, West Lafayette, IN, United StatesDepartment of Neurosurgery, Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN, United StatesSpontaneous 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.https://www.frontiersin.org/article/10.3389/fonc.2019.00780/fullcanine gliomaglioblastomamolecular therapeutic targetsmalignant gliomaanaplastic oligodendroglioma |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Dana Mitchell Sreenivasulu Chintala Kaleigh Fetcko Mario Henriquez Brij N. Tewari Atique Ahmed R. Timothy Bentley Mahua Dey |
spellingShingle |
Dana Mitchell Sreenivasulu Chintala Kaleigh Fetcko Mario Henriquez Brij N. Tewari Atique Ahmed R. Timothy Bentley Mahua Dey Common Molecular Alterations in Canine Oligodendroglioma and Human Malignant Gliomas and Potential Novel Therapeutic Targets Frontiers in Oncology canine glioma glioblastoma molecular therapeutic targets malignant glioma anaplastic oligodendroglioma |
author_facet |
Dana Mitchell Sreenivasulu Chintala Kaleigh Fetcko Mario Henriquez Brij N. Tewari Atique Ahmed R. Timothy Bentley Mahua Dey |
author_sort |
Dana Mitchell |
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 Media S.A. |
series |
Frontiers in Oncology |
issn |
2234-943X |
publishDate |
2019-08-01 |
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. |
topic |
canine glioma glioblastoma molecular therapeutic targets malignant glioma anaplastic oligodendroglioma |
url |
https://www.frontiersin.org/article/10.3389/fonc.2019.00780/full |
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