表面型大腸腫瘍におけるDCC遺伝子コドン201の多型性に関する検討

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  • Codon201Arg/Gly Polymorphism of the DCC (Deleted in Colorectal Carcinoma) Gene in Frat-and Polypoid-Type Colorectal Tumors

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Recent studies have identified the distinct existence of flat-type colorectal tumors. The low incidence of ras gene mutations in these tumors suggests that their genetic pathways of tumor progression may be different from those of the polypoid type. To elucidate further genetic alterations in flat-type colorectal tumors, codon 201^<Arg/Gly> polymorphism in the DCC (deleted in colorectal carcinoma) gene was analyzed in normal tissue (normal colonic mucosa or peripheral lymphocytes), and tumor tissue from 191 patients with colorectal tumors (36 patients with flat-type colorectal tumors, 81 patients with polypoid-type colorectal tumors, and 74 patients with advanced carcinomas) . For normal controls, 30 samples obtained from patients who had neither colorectal tumors (confirmed by total colonoscopy) nor a family history of colorectal carcinoma were analyzed. DCC gene codon 201^<Arg/Gly> polymorphism was investigated by polymerase chain reaction-based restriction fragment length polymorphism analysis, fluorescence-based dideoxy sequencing, or both. For the flat type, the frequency of codon 201^<Gly> of the DCC gene was 64% and 54% in the normal tissue of patients with adenoma with high-grade dysplasia and submucosal carcinoma, respectively. It was 49%, 52%, and 49% in the normal tissue of patients with polypoid-type adenoma with high-grade dysplasia, submucosal carcinoma, and advanced carcinoma, respectively. In the normal tissue, codon 201^<Gly> of the DCC gene was more frequently observed in patients with flat-type adenoma with low-grade dysplasia (67%) than in those with polypoid-type adenoma with low-grade dysplasia (18%) or in normal controls (17%) (p<0.05, x^2 test) . Codon 201^<Arg/Gly> polymorphism in tumor tissues did not differ from that in the corresponding normal tissues, except for ten cases of carcinoma with loss of heterozygosity (LOH). In carcinomas with LOH, preferential loss of the codon 201^<Arg> allele was noted (9/10 cases) . These results suggest that codon 201^<Gly> of the DCC gene is not only associated with flat-type colorectal tumors, but that it may serve as a useful genetic marker for identifying groups at higher risk for colorectal cancer.

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