LOH on 10p14-p15 targets the PFKFB3 gene locus in human glioblastomas.

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 the PFKFB3 gene, located in 10p15.1, inhibits the anchorage-independent growth of U87 glioblastoma cells, we hypothesized that PFKFB3 is a target gene of LOH in glioblastomas. In this study, we analyzed 40 glioblastomas for LOH in 10p15, including the PFKFB3 and KLF6 loci, by PCR-based microsatellite analysis. We detected LOH of PFKFB3 in 55% (22/40) of glioblastomas. LOH of KLF6, mapped 2.5 cM telomerically to the PFKFB3 locus, was not stringently correlated to the PFKFB3 LOH. The allelic deletion of PFKFB3 resulted in a decrease of PFKFB3 mRNA level accompanied by a lower PFKFB3 protein level. The expression of growth-inhibiting splice variant UBI2K4 was effectively reduced in glioblastomas with PFKFB3 LOH and a positive correlation with overall PFKFFB3 expression was observed. The PFKFB3 LOH as well as the resulting low UBI2K4 expression level was associated with a poor prognosis of glioblastoma patients. We conclude that LOH on 10p14-p15 in glioblastomas targets PFKFB3 and in particular splice variant UBI2K4, a putative tumor suppressor protein in glioblastomas.

• Authors: Michael Fleischer, Renate Kessler, Angelika Klammer, Jan-Peter Warnke, Klaus Eschrich
• Journal: Genes, chromosomes & cancer (Genes Chromosomes Cancer) Vol. 50 Issue 12 Pg. 1010-20 (Dec 2011) ISSN: 1098-2264 [Electronic] United States
• PMID: 21987444 (Publication Type: Journal Article)
• Copyright: Copyright © 2011 Wiley-Liss, Inc.

Chemical References

• KLF6 protein, human
• Kruppel-Like Factor 6
• Kruppel-Like Transcription Factors
• Proto-Oncogene Proteins
• RNA, Messenger
• Tumor Suppressor Proteins
• PFKFB3 protein, human
• Phosphofructokinase-2

Topics

• Adult
• Aged
• Aged, 80 and over
• Alleles
• Brain Neoplasms (enzymology, genetics, metabolism)
• Chromosomes, Human, Pair 10
• Female
• Genes, Tumor Suppressor
• Glioblastoma (enzymology, genetics, metabolism)
• Humans
• Kruppel-Like Factor 6
• Kruppel-Like Transcription Factors (genetics, metabolism)
• Loss of Heterozygosity
• Male
• Microsatellite Repeats
• Middle Aged
• Phosphofructokinase-2 (genetics, metabolism)
• Prognosis
• Proto-Oncogene Proteins (genetics, metabolism)
• RNA, Messenger (genetics)
• Tumor Suppressor Proteins (genetics, metabolism)
• Young Adult