KUB3 amplification and overexpression in human gliomas

Gene amplification is known to occur frequently in human glioma. Recently w e reported cloning of a novel gene termed glioma-amplified sequence 16 (GAS 16) by microdissection-mediated cDNA capture. In this article, we demonstra te that GAS16 results from an alternative splicing process of the Ku70 bind ing protein 3 (KUB3) that is essential for DNA double-strand break repair. The alternative splice product was found in glioblastoma and in normal feta l brain. We determined the amplification frequency of KUB3 in glioma with d ifferent grading. We analyzed a total of 102 glioma primary tumors and foun d KUB3 to be amplified in 12/82 (14%) glioblastomas, 4/13 anaplastic astroc ytomas (30%), and 2/4 astrocytomas, but in none of three pilocytic astrocyt omas. Northern blot analysis of glioblastoma shows a strong correlation bet ween KUB3 amplification and overexpression. Amplification of KUB3 appears t o be independent of other genetic changes frequently associated with the de velopment of gliomas, including EGFR amplification, LOH of TP53, and LOH of chromosome 10. The KUB3 amplification and overexpression may interfere wit h the function of KUB3 in the DNA-PK complex involved in the maintenance of genome stability and reduction of mutation frequency. (C) Wiley-Liss, Inc.