KLF6, a putative tumor suppressor gene, is mutated in astrocytic gliomas.
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.
Department of Pathology, National Taiwan University Hospital, No. 7 Chung-Shan Road, Taipei 100, Taiwan.
Yung-Ming
YM
Jeng
Hey-Chi
HC
Hsu
D000328:Adult; D000368:Aged; D000483:Alleles; D019943:Amino Acid Substitution; D001254:Astrocytoma / Q000235:genetics* / Q000473:pathology; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D003062:Codon / Q000235:genetics; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D016147:Genes, Tumor Suppressor; D005909:Glioblastoma / Q000235:genetics / Q000473:pathology; D006801:Humans; D000075723:Kruppel-Like Factor 6; D051741:Kruppel-Like Transcription Factors; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009154:Mutation; D009837:Oligodendroglioma / Q000235:genetics / Q000473:pathology; D017354:Point Mutation; D011518:Proto-Oncogene Proteins; D017422:Sequence Analysis, DNA; D012694:Serine / Q000737:chemistry; D013329:Structure-Activity Relationship; D015534:Trans-Activators / Q000235:genetics* / Q000502:physiology
D003062:Codon; D004273:DNA, Neoplasm; C105465:KLF6 protein, human; D000075723:Kruppel-Like Factor 6; D051741:Kruppel-Like Transcription Factors; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D012694:Serine