GENETIC INSTABILITY AND MUTATION OF THE TGF-BETA-RECEPTOR-II GENE IN AMPULLARY CARCINOMAS

Ampullary carcinomas are relatively rare cancers of which very little is known in terms of carcinogenetic mechanisms at the molecular level. Genetic instability caused by mutations of mismatch-repair genes has been demonstrated to be responsible for hereditary non-polyposis color ectal cancers and a sub-set of sporadic colorectal cancers. In some of those tumors showing genetic instability, the transforming-growth-fac tor-beta (TGF-beta)-receptor-II gene has been found to be mutated in r epetitive sequences and considered to be a target of replication error . We studied the role of genetic instability and associated TGF-beta-r eceptor-II-gene mutations in a series of 18 sporadic cases by analyzin g 5 microsatellite loci (D2S123, D3S1029, D5S409, TP53 and BAT26) and by sequencing a poly-A repeat (nucleotides 709-718) in the TGF-beta-re ceptor-II gene. Microsatellite instability was observed in 4 (22.2%) a nd gene mutations in 14 (77.8%) cases. These data indicate that the TG F-beta-receptor-II gene might be a preferential target of genetic inst ability whose alteration might be specifically advantageous and consti tute a common step in the development of ampullary carcinomas. (C) 199 8 Wiley-Liss, Inc.