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

Abstract

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.

KLF6 Suppresses Metastasis of Clear Cell Renal Cell Carcinoma via Transcriptional Repression of E2F1

“…The Kr€ uppel-like factor 6 (KLF6) gene is a tumor suppressor that is deregulated and inactivated by gene loss or somatic mutation in various cancers, such as colorectal cancer (6), prostate cancer (7), and glioblastoma (8). Our previous tissue profiling results indicated that KLF6 was significantly downregulated in metastatic specimens.…”

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

“…In contrast with the other studies, they only analyzed exon 2. None of the other studies included methods to [10][11][12][13] (ranging between 0 and 15%) and colorectal carcinoma [14][15][16][17][18] (ranging between 0 and 44%). Similar to prostate cancer, the first studies conducted on these other tumors indicated a high frequency of mutation, but this was not reproduced in subsequent reports.…”

“…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%.…”

KLF6 transcription factor protects hepatocellular carcinoma-derived cells from apoptosis

“…17 However, the extent of KLF6 loss in major human cancers has been recently subjected to passionate debate. Numerous studies now report the absence of somatic mutation nor KLF6 inactivation in colorectal carcinoma, 27 in glioblastomas, 28 in prostate cancer, 29,30 in meningiomas, 28,31 in astrocytic tumors, 32 and, finally, in HCC. 18 Here, we confirmed that KLF6 is not mutated, and expressed in HCC samples, and in HCC-derived cell lines.…”