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A Specific Genetic Alteration on Chromosome 6 in Ulcerative Colitis-associated Colorectal Cancers¹

Department of Internal Medicine [T. E., H. O., H. I., T. H.] and Center for Comprehensive and Advanced Medicine [N. I., Y. I., T. H.], School of Medicine, Keio University, Shinjuku-ku, Tokyo 160-8582, Japan, and Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8589, Japan [M. W., T. K.]

Various genetic alterations in ulcerative colitis (UC)-associated colorectal cancers (CRCs) have been reported. However, almost all studies have shown abnormalities of the known genes that have been demonstrated in sporadic CRCs. To identify novel genetic alterations, we selected unintentionally 35 microsatellite markers, and performed allelotype study in CRCs or dysplastic lesions from UC. High frequency of loss of heterozygosity (LOH; 62.5%) was detected on chromosome 6 (D6S468) but not on other chromosomes. With four additional microsatellite markers around the D6S468 locus, we determined the commonly deleted region between two loci, D6S1543 and D6S1580, in UC-associated CRCs and dysplasia. Interestingly, there was no LOH in this region in sporadic CRCs and severely inflamed lesions of longstanding and extensive UC without cancers. These results indicated the presence of novel tumor suppressor genes on chromosome 6 related to the carcinogenesis of UC but not to sporadic CRCs.