SOMATICALLY ACQUIRED GENETIC ALTERATIONS IN FLAT COLORECTAL NEOPLASIAS

Somatically acquired mutations in several genes have been reported as playing an important role during colorectal tumorigenesis, Two alterna tive groups of carcinomas, termed LOH+ and RER+, have been defined on the basis of their genetic anomalies, a biallelic inactivation of the APC or the TGF-beta RII genes, occurring as an alternative, in LOH+ or RER+ tumors. It is a generally accepted hypothesis that most of color ectal cancers (CRC) develop from a pre-existing adenomatous polyp. Suc h benign lesions are usually exophytic polyps, a small proportion of a denomas having been described as flat lesions. The latter histological category has thus been proposed to bear specific genetic alterations. In order to examine this hypothesis, we have characterized a series o f 44 flat colorectal neoplasias for their RER status and for somatic A PC, KRAS and TGF-beta RII genes mutations. Flat colorectal neoplasias were found to be of the RER+ subtype in 22% of cases, all of them exhi biting a TGF-beta RII mutation. A mutation of the APC and KRAS genes h as been found in 42% and 4% of tumors, respectively, none of these tum ors being of the RER+ subtype, With the exception of a low KRAS mutati on rate, flat adenomas appear to follow tumorigenesis pathways very si milar to those identified in exophytic adenomas and carcinomas. (C) 19 98 Wiley-Liss, Inc.