Loss of heterozygosity (LOH) on chromosome 10 is the most common genetic changes in glioblastomas of World Health Organization (WHO) Grade IV. [1][2][3][4][5][6][7] In most cases, the allelic losses involve loci along the entire chromosome, a finding in line with monosomy 10. LOH on chromosome 10 may also be detected in anaplastic astrocytomas (WHO Grade III) and diffuse astrocytomas (WHO Grade II), but is less common than in glioblastomas and more frequently restricted to partial losses. 7 In astrocytomas with partial LOH of chromosome 10, 3 regions, i.e., 10p14 -pter, 10q23-q24 and 10q25-qter, have been identified. 8,9 Whereas the PTEN/ MMAC1 tumor suppressor gene (TSG) at 10q23 is mutated in approximately one-third of glioblastomas, 10 target genes for 10p14 -pter and 10q25-qter remain undiscovered. At 10p15, the presence of a TSG has been suggested by a cell fusion study, 11 and introduction of 10p15 chromosomal fragment into glioblastoma cell line T98G suppressed colony formation in soft agar. 12 A candidate TSG, KLF6 (Kru Β¨ppel-like factor 6) on chromosome 10p15, undergoes alterations in up to 55% of prostate carcinomas by deletion, point mutations and loss of expression. 13,14 KLF6 is a transcription factor involved in the regulation of cell proliferation and differentiation. Moreover, functional studies showed that, whereas wild-type KLF6 upregulates p21 (WAF1/CIP1) in a p53-independent manner and leads to reduced cell proliferation, tumor-derived KLF6 mutants do not. 13 In a recent study, 15 mutations of KLF6 were found in Grade II-IV astrocytic brain tumors. We therefore investigated the possible involvement of KLF6 in astrocytoma formation by detecting its mutations in an independent tumor series. No mutation was detected in 52 astrocytomas of various WHO grades and 30 glioma cell lines, questioning the role of KLF6 in brain tumor development.
We obtained formalin-fixed, paraffin-embedded tumor specimens from 52 patients who were diagnosed and operated for astrocytomas at the Tampere University Hospital between 1991-2001. These included 10 pilocytic astrocytomas (WHO Grade I), 9 WHO Grade II astrocytomas, 11 anaplastic astrocytomas (WHO Grade III), and 22 glioblastomas (WHO Grade IV). Snap-frozen tumor samples were also available for 30 of the samples (WHO Grade I, 10 tumors; WHO Grade II, 3 tumors; WHO Grade III, 1 tumor; WHO Grade IV, 16 tumors).