ADENOMATOUS POLYPOSIS-COLI GENE-MUTATIONS IN ULCERATIVE COLITIS-ASSOCIATED DYSPLASIAS AND CANCERS VERSUS SPORADIC COLON NEOPLASMS

Adenomatous polyposis coli (APC) gene mutations occur in most sporadic colonic adenomas and carcinomas, Precursor lesions of ulcerative coli tis (UC)-associated colon carcinomas, although morphologically similar to sporadic adenomas, may be biologically distinct from them and are, in fact, managed differently, Since sporadic adenomas may also occur in UC, a method of discriminating between these forms of neoplasia cou ld have clinical utility, We examined 33 patients with UC-associated d ysplasias and cancers and 23 sporadic colon neoplasms in a side-by-sid e comparison for APC mutations, Codons 686-1693, containing 64% of all reported APC mutations (the mutation cluster region), were screened f or truncating mutations using an in vitro synthesized protein assay, T wo of thirty-three patients (6%) with UC-associated dysplasias and can cers had a total of three truncating APC mutations, all in frank carci nomas, while 17 of 23 (74%) with sporadic colonic neoplasms had mutati ons. DNA sequencing confirmed two mutations in codon 1460, replacing a rginine with a stop codon, as well as one 2-base pair deletion, result ing in a frameshift and a stop at codon 1477. One specimen contained o ne each of these APC mutations, This apparent contrast in mutation rat es at the mutation cluster region of APC is consistent with other biol ogical characteristics separating sporadic colon neoplasms from UC-ass ociated dysplasias and cancers, These data raise the possibility that nonadenomatous UC dysplasias may arise by a molecular pathway distinct from that prevailing in sporadic colon carcinogenesis, and they sugge st a molecular assay to discriminate between sporadic adenomas and dys plasias occurring in UC.