title: 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: Institute of Biochemistry, Medical Faculty, University of Leipzig, Leipzig, Germany.
authors: Michael
authors: M
authors: Fleischer
authors: Renate
authors: R
authors: Kessler
authors: Angelika
authors: A
authors: Klammer
authors: Jan-Peter
authors: JP
authors: Warnke
authors: Klaus
authors: K
authors: Eschrich
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001932:Brain Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D002879:Chromosomes, Human, Pair 10; D005260:Female; D016147:Genes, Tumor Suppressor; D005909:Glioblastoma / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D000075723:Kruppel-Like Factor 6; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D025481:Phosphofructokinase-2 / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: C105465:KLF6 protein, human; D000075723:Kruppel-Like Factor 6; D051741:Kruppel-Like Transcription Factors; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; C107345:PFKFB3 protein, human; D025481:Phosphofructokinase-2