HYPERMETHYLATION OF THE WT1 AND CALCITONIN-GENE PROMOTER REGIONS AT CHROMOSOME 11P IN HUMAN COLORECTAL-CANCER

The short arm of the chromosome 11, known to harbour a number of putat ive and established tumour-suppressor genes, is frequently hypermethyl ated in various human neoplasms. We subjected the promoter regions of two genes residing at 11p, namely the tumour-suppressor gene WT1 (Wilm s' tumour gene) (11p13) and the calcitonin gene (11p15.5), to methylat ion analysis in human sporadic colorectal cancer using genomic sequenc ing. Both genes showed significant hypermethylation of CpG sites withi n their promoter regions in adenomas and carcinomas compared with norm al colonic mucosa. Although the WT1 promoter region was significantly hypermethylated, two CPG sites located in Spl motifs were unmethylated in the majority of cases (68-74% of carcinomas). The expression of WT 1 gene, as revealed by in situ hybridization, showed no differences be tween normal colonic mucosa and malignant carcinoma. Together with ear lier observations, our present results support the view that the short arm of human chromosome 11 is subjected to widespread regional hyperm ethylation in various human malignancies.