Media type: E-Article Title: LOH on 10p14‐p15 targets the PFKFB3 gene locus in human glioblastomas Contributor: Fleischer, Michael; Kessler, Renate; Klammer, Angelika; Warnke, Jan‐Peter; Eschrich, Klaus imprint: Wiley, 2011 Published in: Genes, Chromosomes and Cancer Language: English DOI: 10.1002/gcc.20914 ISSN: 1045-2257; 1098-2264 Keywords: Cancer Research ; Genetics Origination: Footnote: Description: <jats:title>Abstract</jats:title><jats:p>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 (<jats:italic>KLF6</jats:italic>) has been suggested as possible target of LOH in this region. On the basis of the fact that the splice variant 4 (<jats:italic>UBI2K4</jats:italic>) of the <jats:italic>PFKFB3</jats:italic> gene, located in 10p15.1, inhibits the anchorage‐independent growth of U87 glioblastoma cells, we hypothesized that <jats:italic>PFKFB3</jats:italic> is a target gene of LOH in glioblastomas. In this study, we analyzed 40 glioblastomas for LOH in 10p15, including the <jats:italic>PFKFB3</jats:italic> and <jats:italic>KLF6</jats:italic> loci, by PCR‐based microsatellite analysis. We detected LOH of <jats:italic>PFKFB3</jats:italic> in 55% (22/40) of glioblastomas. LOH of <jats:italic>KLF6</jats:italic>, mapped 2.5 cM telomerically to the <jats:italic>PFKFB3</jats:italic> locus, was not stringently correlated to the <jats:italic>PFKFB3</jats:italic> LOH. The allelic deletion of <jats:italic>PFKFB3</jats:italic> resulted in a decrease of <jats:italic>PFKFB3</jats:italic> mRNA level accompanied by a lower <jats:italic>PFKFB3</jats:italic> protein level. The expression of growth‐inhibiting splice variant <jats:italic>UBI2K4</jats:italic> was effectively reduced in glioblastomas with <jats:italic>PFKFB3</jats:italic> LOH and a positive correlation with overall PFKFFB3 expression was observed. The <jats:italic>PFKFB3</jats:italic> LOH as well as the resulting low <jats:italic>UBI2K4</jats:italic> expression level was associated with a poor prognosis of glioblastoma patients. We conclude that LOH on 10p14‐p15 in glioblastomas targets <jats:italic>PFKFB3</jats:italic> and in particular splice variant <jats:italic>UBI2K4</jats:italic>, a putative tumor suppressor protein in glioblastomas. © 2011 Wiley Periodicals, Inc.</jats:p>