A TRANSFORMING GROWTH-FACTOR-BETA-1 RECEPTOR-TYPE-II MUTATION IN ULCERATIVE COLITIS-ASSOCIATED NEOPLASMS

Background & Aims: Numerous gastrointestinal tumors, notably sporadic and ulcerative colitis (UC)-associated colorectal carcinomas and dyspl asias, gastric cancers, and esophageal carcinomas, manifest microsatel lite instability, Recently, a transforming growth factor beta 1 type I I receptor (TGF-beta 1RII) mutation in a coding microsatellite was des cribed in colorectal carcinomas showing instability, One hundred thirt y-eight human neoplasms (61 UC-associated, 35 gastric, 26 esophageal, and 16 sporadic colorectal) were evaluated for this TGF-beta 1RII muta tion, Methods: Whether instability was present at other chromosomal lo ci in these lesions was determined, In lesions manifesting or tacking instability, the TGF-beta 1RII coding region poly-deoxyadenine (poly A ) microsatellite tract was polymerase chain reaction amplified with P- 32-labeled deoxycytidine triphosphate. Polymerase chain reaction produ cts were electrophoresed on denaturing gels and exposed to radiographi c film, Results: Three of 18 UC specimens with instability at other ch romosomal loci (17%) showed TGF-beta 1RII poly A tract mutation, inclu ding 2 cancers and 1 dysplasia; moreover, 2% of UC specimens without i nstability (1 of 43) (1 cancer), 81% of unstable sporadic colorectal c ancers (13 of 16), and none of the 61 stable or unstable gastric or es ophageal cancers contained TGF-beta 1RII mutations. Conclusions: Mutat ional inactivation of the poly A microsatellite tract within TGF-beta 1RII occurs early and in a subset of unstable UC neoplasms and commonl y in sporadic colorectal cancers but may be rare in unstable gastric a nd esophageal tumors.