Role of KLF6 tumor suppressor gene mutations in the development of colorectal carcinoma in an Egyptian population.

BACKGROUND/AIMS: Colorectal cancer is one of the common cancers of the gastrointestinal tract in Egypt. It is characterized by a relatively earlier onset compared to that in the western world. Studying genetic alterations involved in colorectal cancer progression may help in identifying molecular biomarkers that can be used for early detection.

METHODOLOGY

We analyzed DNA isolated from 83 cases including 38 colorectal carcinomas, 23 polyps (16 of which were adenomatous) and 22 cases with inflammatory bowel disease (IBD). Mutations at KLF6 tumor suppressor gene (exon 1-4) were examined by PCR-SSCP silver staining technique followed by direct sequencing. 10p15 LOH was analyzed using KLF6 M1, KLF6 M2 and KLF6 M4 markers by microsatellite assay.

RESULTS

KLF6 mutations were found in 45%, 27% and 26% of colorectal carcinoma, ulcerative colitis and polyp cases, respectively. Most of the mutations detected were located at exon 2. The majority of mutations found in KLF6 were missense mutation and their type and locations were different from those previously described in the western population. The frequencies of LOH at the three markers examined were 29%, 36%, and 52% for colorectal carcinomas, IBD, and polyp cases, respectively. LOH was detected in mutant KLF6 as well as wild type. No significant association was found between genetic alterations examined with different clinicopathological factors.

CONCLUSIONS

Our data highlights for the first time an association of KLF6 gene in colorectal cancer in an Egyptian population. Detecting mutational sites different from those in western population is a characteristic feature in our study which may be related to environmental and/or genetic factors that have to be further identified.