LOH on 10p14-p15 targets thePFKFB3gene locus in human glioblastomas

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Abstract

Loss of heterozygosity (LOH) on chromosome arm 10p is very common in high-grade gliomas and is, among others, concentrated on the region 10p14-p15. Presence of multiple tumor suppressor genes is assumed, but until now only Krüpple-like transcription factor 6 (KLF6) has been suggested as possible target of LOH in this region. On the basis of the fact that the splice variant 4 (UBI2K4) of thePFKFB3gene, located in 10p15.1, inhibits the anchorage-independent growth of U87 glioblastoma cells, we hypothesized thatPFKFB3is a target gene of LOH in glioblastomas. In this study, we analyzed 40 glioblastomas for LOH in 10p15, including thePFKFB3andKLF6loci, by PCR-based microsatellite analysis. We detected LOH ofPFKFB3in 55% (22/40) of glioblastomas. LOH ofKLF6, mapped 2.5 cM telomerically to thePFKFB3locus, was not stringently correlated to thePFKFB3LOH. The allelic deletion ofPFKFB3resulted in a decrease ofPFKFB3mRNA level accompanied by a lowerPFKFB3protein level. The expression of growth-inhibiting splice variantUBI2K4was effectively reduced in glioblastomas withPFKFB3LOH and a positive correlation with overall PFKFFB3 expression was observed. ThePFKFB3LOH as well as the resulting lowUBI2K4expression level was associated with a poor prognosis of glioblastoma patients. We conclude that LOH on 10p14-p15 in glioblastomas targetsPFKFB3and in particular splice variantUBI2K4, a putative tumor suppressor protein in glioblastomas. © 2011 Wiley Periodicals, Inc.

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