Work

Pcm-07comparative Genomics: the Dog as a Translational Model for Meningioma

Year: 2016

Type: article

Abstract: INTRODUCTION: Meningiomas are the most common primary brain tumor in humans and in dogs, accounting for almost half of all primary intracranial neoplasms in dogs. Tumor locations, imaging characteristics, histopathologic analysis, presenting symptoms all suggest that the canine and human diseases have a common molecular basis. We propose a unique brain tumor model for translational studies based on molecular findings. METHODS: Illumina Infinium HD bead chip genetic mapping was performed on 54 sporadic canine meningiomas from pet dogs presented to two Colleges of Veterinary Medicine between 2004 and 2012. Published canine genome data were used to search for copy number variations among 37 canine autosomal linkage groups in tumors and normal brain samples. RESULTS: The most common amplifications and deletions in aggressive tumors, not seen in histologically benign meningiomas, included 32 candidate genes in deleted regions of four linkage groups. Regions of segmental DNA with amplifications and deletions in tumors not found in matched normal brain tissue were parsed to identify six candidate therapeutic target genes: TREM1, PIM1, SLC34B2, VEGFA, RPS27A, CD34 and B3GAT1. Four are on canine linkage group 6 and also on human linkage group 12. Copy number variations seen among these canine tumors are also known to be present in human meningiomas. Functions of these genes relevant to tumor development and progression are being tested. CONCLUSION: The dog offers a tractable translational model for comparative analyses of spontaneous canine and sporadic human meningiomas, suitable for assessment and development of current and novel therapies based on molecular targets.

Source: Neuro-Oncology

DOI: 10.1093/neuonc/now080.07