Absence of mutation in the putative tumor-suppressor gene KLF6 in colorectal cancers.
The KLF6 gene encodes the Krüppel-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.
Lièvre
Astrid
A
1INSERM U490 Laboratoire de Toxicologie Moléculairei, Université René Descartes, 75006 Paris, France. pierre.laurent-puig@univ-paris5.fr
Landi
Bruno
B
Côté
Jean-François
JF
Veyrie
Nicolas
N
Zucman-Rossi
Jessica
J
Berger
Anne
A
Laurent-Puig
Pierre
P
D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics; D002879:Chromosomes, Human, Pair 10; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D005091:Exons; D005260:Female; D016147:Genes, Tumor Suppressor; D014644:Genetic Variation; D018095:Germ-Line Mutation; D006801:Humans; D007438:Introns; D000075723:Kruppel-Like Factor 6; D051741:Kruppel-Like Transcription Factors / Q000235:genetics*; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D009154:Mutation; D009367:Neoplasm Staging; D021141:Nucleic Acid Amplification Techniques; D020641:Polymorphism, Single Nucleotide; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA; D016335:Zinc Fingers
D014408:Biomarkers, Tumor; C105465:KLF6 protein, human; D000075723:Kruppel-Like Factor 6; D051741:Kruppel-Like Transcription Factors; D011518:Proto-Oncogene Proteins