Chromosomal gain and mutations ofgene in canine high-grade oligodendroglioma.

Abstract

Canine high-grade oligodendrogliomas (HGOGs) exhibit a high expression of platelet-derived growth factor receptor-&#x3b1; (PDGFRA). We examinedmutations and gain ofand their association with the PDGFRA expression and proliferation of tumor cells in canine HGOG cases and cell lines. Polymerase chain reaction and sequence analysis revealed expected pathogenic mutations inexons 7 and 8 in 16/34 (47%) cases. However, these mutations were not associated with PDGFRA expression, as examined by mRNAhybridization (ISH) and immunohistochemistry, or proliferation activity, as examined by the Ki-67 labeling index (LI). Chromosomal ISH performed in 16 cases revealedand() gains in 15 cases (94%).gain was moderately correlated withmRNA expression (&#x3c1; = 0.54,= .04) and were moderately correlated with PDGFRA H-score, which is the score based on immunolabeling intensity (&#x3c1; = 0.44,= .09). However,gain was not correlated with the Ki-67 LI (&#x3c1; = 0.23,= .38). The canine HGOG cell line withgain showed highermRNA expression (< .01), H-score (< .01), and Ki-67 LI (< .01) than the cell line withoutgain. The gain ofandsuggests polysomy of canine chromosome 13, where both genes are located. Theanalysis results suggested that chromosome 13 polysomy is associated with increased PDGFRA expression and cell proliferation in canine HGOG. Chromosome 13 polysomy may be involved in canine gliomagenesis by increasing PDGFRA expression and inducing tumor cell proliferation.