Absence of mutations in the putative tumor suppressor gene <i>KLF6</i> in glioblastomas and meningiomas

Köhler, Benjamin; Wolter, Marietta; Blaschke, Britta; Reifenberger, Guido

doi:10.1002/ijc.20302

Cited by 22 publications

(16 citation statements)

References 11 publications

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“…Two of these polymorphims (G3023A and R201R) had been already reported (Kohler et al, 2004;Koivisto et al, 2004a, b;Montanini et al, 2004;Reeves et al, 2004;Boyault et al, 2005). We did not find mutation in KLF6 exon 2 in any of the 76 tumor samples analysed.…”

supporting

confidence: 68%

“…Indeed, no mutation was found in a larger series of hepatocellular carcinoma by another group (Boyault et al, 2005). Finally, astrocytic gliomas show the same difference with no mutation found in three different studies (Kohler et al, 2004;Koivisto et al, 2004b;Montanini et al, 2004) after a first report that described 9% of KLF6 mutations in the exon 2 (Jeng and Hsu, 2003).…”

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confidence: 60%

“…In this way, it is interesting to note that no mutation were identified in four CRC cell lines (SW480, HCT115, HCT116 and HT29) analysed in the study by Reeves et al (2004). This argument of artefactual mutations caused by formalin-fixation has already been raised to explain the discrepant results obtained for KLF6 mutations in astrocytic gliomas (Kohler et al, 2004). KLF6 allelic loss was found in 9% of the cases and may be another mechanism of KLF6 inactivation as it was reported Figure 2 Data of the five tumors that had loss of at least two markers, consistent with KLF6 LOH.…”

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confidence: 88%

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Absence of mutation in the putative tumor-suppressor gene KLF6 in colorectal cancers

et al. 2005

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The KLF6 gene encodes the Kru¨ppel-like factor 6, a transcription factor that has been individualized as a tumor-suppressor gene involved in the regulation of cell proliferation and differentiation. Recently, high frequency (42%) of KLF6 mutations have been reported in colorectal cancers (CRC) as in prostate cancers, astrocytic gliomas and hepatocellular carcinomas. The aims of the study was to confirm the frequency of KLF6 mutations in a larger series of CRC than that previously published by using DNA extracted from frozen tissue samples, which have been proved to generate less mutational artefact than that extracted from formalin-fixed paraffin-embedded tissue samples, in order to compare KLF6 mutation frequency with that of other common genetic alterations and to determine genotype-phenotype correlations. Amplification and direct sequencing of KLF6 exon 2 of 76 CRC and matched normal frozen tissues was performed. Polymorphisms were observed in 14 cases, among which two (T35T and S116S) had not already been reported. No KLF6 somatic mutation was observed. Our data suggest a minor role of KLF6 mutation in colorectal carcinogenesis and underline the fact that the validity of sequence informations obtained from DNA extracted from formalin-fixed tissues may be limited.

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confidence: 68%

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confidence: 60%

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confidence: 88%

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Absence of mutation in the putative tumor-suppressor gene KLF6 in colorectal cancers

et al. 2005

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“…So the highly variable frequency of KLF6 mutations may be caused by differences in methodology and sample sets. For example, some reports showed that KLF6 mutations are absent in prostate cancers (Mühlbauer et al, 2003) and human astrocytic gliomas (Koivisto et al, 2004;Köhler et al, 2004;Montanini et al, 2004), while other authors reported high frequencies of KLF6 mutations in prostate cancer (55%) (Narla et al, 2001) and astrocytic gliomas (9%) (Jeng and Hsu, 2003). Therefore, extensive investigation in both HCC and other human cancers is needed to determine the frequency of KLF6 mutation and its role in hepatocarcinogenesis.…”

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confidence: 99%

Inactivation of the tumor suppressor Krüppel-like factor 6 (KLF6) by mutation or decreased expression in hepatocellular carcinomas

Pan

Chen

et al. 2006

J. Zhejiang Univ. - Sci. B

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Background and aim: The Krüppel-like transcription factor KLF6 is a novel tumor-suppressor gene. It was inactivated in human prostate cancer and other tumors tissue, as the result of frequent mutation and loss of heterozygosity (LOH). However, there is no data reporting the levels of KLF6 both mRNA and protein in hepatocellular carcinomas (HCCs). We therefore detected mutations and expression of KLF6 in HCC tissues and further observed the effect of it on cell growth in HCC cell lines. Methods: We analyzed the exon-2 of KLF6 gene by direct DNA sequencing, and detected the expression of KLF6 by RT-PCR and Western blot in 23 HCC tissues and corresponding nontumorous tissues. Loss of growth suppressive effect of the HCC-derived KLF6 mutant was characterized by in vitro growth curves plotted, flow cytometry and Western blotting. Results: KLF6 mutations were found in 2 of 23 HCC tissues and one of mutations was missense. Expression of KLF6 mRNA or protein was down-regulated in 8 (34.7%) or 9 (39.1%) of 23 HCC tissues. Wild-type KLF6 (wtKLF6) inhibited cellular proliferation and prolonged G1-S transition by inducing the expression of p21WAF1 following stable transfection into cultured HepG2 cells, but tumor-derived KLF6 mutant (mKLF6) had no effects. Conclusion: Our findings suggest that KLF6 may be involved in pathogenesis of HCC.

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“…9 The reported frequency of KLF6 mutations in different types of human cancer varies in the different published studies. [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] In prostate cancer, four studies have analyzed the frequency of KLF6 mutations. 6,[30][31][32] In the first published study, Narla et al 6 showed a very high frequency, 55%, whereas in the following study, Chen et al 30 obtained a lower frequency, around 15%.…”

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KLF6 and TP53 mutations are a rare event in prostate cancer: distinguishing between Taq polymerase artifacts and true mutations

et al. 2008

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Krü ppel-like factor 6 (KLF6) has been reported to act as a tumor suppressor gene involved in the regulation of the cell cycle by activating p21 in a p53-independent manner. Many studies suggest that KLF6 is inactivated by allelic loss and somatic mutation. However, there is a high variability in the reported frequency of mutations (from 1 to 55%). TP53 also regulates the cell cycle through the activation of p21. In prostate cancer, the reported frequency of TP53 mutations ranges from 3 to 42%. In all these reports, there is a considerable degree of methodological heterogeneity. Our aim was to determine the frequency of KLF6 and TP53 mutations in a welldefined group of prostate tumors with different stages and Gleason grades. The four exons of KLF6 and exons 4-9 of TP53 were studied in 103 cases, including 90 formalin-fixed, paraffin-embedded (FFPE) and 13 frozen samples. All tumors were analyzed through PCR and direct sequencing. All changes found were confirmed by a second independent PCR and sequencing reaction. For KLF6, mutation (E227G) was only detected in one tumor (1%) and for TP53, three different mutations (L130H, H214R, and Y234C) were detected in five tumors (5%). This low mutation index is in keeping with recent papers on the subject. Our study strongly supports the notion that KLF6 and TP53 mutations are not frequent events in prostate cancer. When using FFPE tissues, it is mandatory to perform at least two independent rounds of PCR and sequencing to confirm mutations and exclude Taq polymerase-induced artifacts. Two of these genes are Krü ppel-like factor 6 (KLF6) and TP53.KLF6 is a transcription factor that interacts with DNA through three zinc-fingers in its COOHterminal domain. KLF6 belongs to the KLF family, a family that is broadly involved in cell differentiation, development, growth-related signal transduction, cell proliferation, apoptosis, and angiogenesis. 5 It has been suggested that KLF6 could be involved in the regulation of the cell cycle by activating p21 in a p53-independent manner. 6 This has been proven in several in vitro 5 and in vivo assays. 7 KLF6 is believed to regulate cancer development and progression through the downregulation of the c-Jun oncoprotein 8 and the activation of E-cadherin. 9 The reported frequency of KLF6 mutations in different types of human cancer varies in the different published studies. [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] In prostate cancer, four studies have analyzed the frequency of KLF6 mutations. 6,[30][31][32] In the first published study, Narla et al 6 showed a very high frequency, 55%, whereas in the following study, Chen et al 30 obtained a lower frequency, around 15%. The results of two recent reports provided frequencies of 0 and 1%. 31,32 It should be noted that there were considerable

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Absence of mutations in the putative tumor suppressor gene KLF6 in glioblastomas and meningiomas

Cited by 22 publications

References 11 publications

Absence of mutation in the putative tumor-suppressor gene KLF6 in colorectal cancers

Absence of mutation in the putative tumor-suppressor gene KLF6 in colorectal cancers

Inactivation of the tumor suppressor Krüppel-like factor 6 (KLF6) by mutation or decreased expression in hepatocellular carcinomas

KLF6 and TP53 mutations are a rare event in prostate cancer: distinguishing between Taq polymerase artifacts and true mutations

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