KLF6, a putative tumor suppressor gene, is mutated in astrocytic gliomas
Journal
International Journal of Cancer
Journal Volume
105
Journal Issue
5
Pages
625-629
Date Issued
2003
Author(s)
Hsu H.-C.
Abstract
Gliomas are the most common tumors of the central nervous system and have a grave prognosis. Deletion of chromosome 10p15 is one of the most common chromosomal alterations in gliomas. Recently, a candidate tumor suppressor gene, KLF6, which is mapped to chromosome 10p, was found to be frequently mutated in prostate cancer. KLF6 is a zinc finger transcription factor and transactivates p21/WAF1/CIP expression. To elucidate the role of genetic alterations of KLF6 in gliomas, we analyzed the 4 exons of the gene by direct DNA sequencing in 155 gliomas. Of these, mutations of KLF6 were found in 9 of 76 (11.8%) glioblastomas multiforme, 2 of 28 (7.1%) anaplastic astrocytomas, 2 of 36 (5.5%) low-grade diffuse astrocytomas and in none of the 15 oligodendrogliomas. All 13 mutations were located in the transactivation domain and most of them affected either serine residues or codons next to serine residues. Of the 13 cases with KLF6 mutation, loss of heterozygosity (LOH) at the KLF6 locus was inferred from the LOH displayed by the flanking microsatellite markers in 11 cases. We conclude that mutations of the KLF6 gene play a role in the pathogenesis of astrocytic gliomas. ? 2003 Wiley-Liss, Inc.
SDGs
Other Subjects
DNA; kruppel like factor 6; microsatellite DNA; transcription factor; unclassified drug; adult; aged; amino acid substitution; article; astrocytoma; brain tumor; central nervous system tumor; female; gene expression; genetic transcription; glioblastoma; glioma; heterozygosity loss; human; human tissue; major clinical study; male; nucleotide sequence; oligodendroglioma; point mutation; polymerase chain reaction; priority journal; transactivation; tumor suppressor gene; Adult; Aged; Alleles; Amino Acid Substitution; Astrocytoma; Brain Neoplasms; Chromosomes, Human, Pair 10; Codon; DNA Mutational Analysis; DNA, Neoplasm; Exons; Female; Genes, Tumor Suppressor; Glioblastoma; Humans; Kruppel-Like Transcription Factors; Loss of Heterozygosity; Male; Microsatellite Repeats; Middle Aged; Mutation; Oligodendroglioma; Point Mutation; Proto-Oncogene Proteins; Sequence Analysis, DNA; Serine; Structure-Activity Relationship; Trans-Activators
Type
journal article