13 May Dog Genome Can Be Used To Identify Human Brain Tumor Genes
MedicalResearch.com Interview with:
Katarina Truvé PhD
Swedish University of Agricultural Sciences and
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Truvé: Gliomas are malignant brain tumors that are rarely curable. These tumors occur with similar frequencies in both dogs and humans. Gliomas in dogs are strikingly similar at the biological and imaging level to human tumor counterparts. Some dog breeds such as Boxer and Bulldog are at considerably higher risk of developing glioma. Since these breeds at high risk are recently related, they are most likely carrying shared genetic risk factors. Our goal was therefore to use the dog genome to locate genes that may be involved in the development of glioma in both dogs and humans. We found a strongly associated locus and identified three candidate genes, DENR, P2RX7 and CAMKK2 in the genomic region. We have shown that CAMKK2 is lower expressed in glioma tumors than normal tissue in both dogs and human, and it has been reported that the associated canine mutation in P2RX7 results in a decrease in receptor function.
MedicalResearch.com: What should readers take away from your report?
Dr. Truvé: We have shown that the dog genome can be used as a model to identify genes that may be of importance for development of glioma in both dogs and humans, but further functional studies are needed to understand the role of the genes identified here.
MedicalResearch.com: What recommendations do you have for future research as a result of this study
Dr. Truvé: At present studies are ongoing to explore the effect of decreased P2RX7 function on carcinogenesis in the canine brain. Since CAMKK2 is lower expressed in tumors than normal brain we suggest to explore methods and effects of increasing the expression of this gene. CAMKK2 and P2RX7 are also expressed in microglia the resident immune cells of the brain. It could be of importance to explore the different roles of these genes in tumor cells versus immune cells since it has been reported that immune factors can have important roles both in defense against and in development of tumors. Furthermore the three genes identified here can come in different splice variants so a more detailed investigation of difference in expression of different variants might also be helpful in exploring the roles of these genes in tumor development.
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Katarina Truvé, Peter Dickinson, Anqi Xiong, Daniel York, Kartika Jayashankar, Gerli Pielberg, Michele Koltookian, Eva Murén, Hans-Henrik Fuxelius, Holger Weishaupt, Fredrik J. Swartling, Göran Andersson, Åke Hedhammar, Erik Bongcam-Rudloff, Karin Forsberg-Nilsson, Danika Bannasch, Kerstin Lindblad-Toh.
Utilizing the Dog Genome in the Search for Novel Candidate Genes Involved in Glioma Development—Genome Wide Association Mapping followed by Targeted Massive Parallel Sequencing Identifies a Strongly Associated Locus.
PLOS Genetics, 2016; 12 (5): e1006000 DOI:10.1371/journal.pgen.1006000
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