title: A transforming growth factor beta 1 receptor type II mutation in ulcerative colitis-associated neoplasms.
abstract: OBJECTIVE
  Numerous gastrointestinal tumors, notably sporadic and ulcerative colitis (UC)-associated colorectal carcinomas and dysplasias, gastric cancers, and esophageal carcinomas, manifest microsatellite instability. Recently, a transforming growth factor beta 1 type II receptor (TGF-beta 1RII) mutation in a coding microsatellite was described in colorectal carcinomas showing instability. One hundred thirty-eight human neoplasms (61 UC-associated, 35 gastric, 26 esophageal, and 16 sporadic colorectal) were evaluated for this TGF-beta 1RII mutation.
  
  
  METHODS
  Whether instability was present at other chromosomal loci in these lesions was determined. In lesions manifesting or lacking instability, the TGF-beta 1RII coding region polydeoxyadenine (poly A) microsatellite tract was polymerase chain reaction amplified with 32P-labeled deoxycytidine triphosphate. Polymerase chain reaction products were electrophoresed on denaturing gels and exposed to radiographic film.
  
  
  RESULTS
  Three of 18 UC specimens with instability at other chromosomal loci (17%) showed TGF-beta 1RII poly A tract mutation, including 2 cancers and 1 dysplasia; moreover, 2% of UC specimens without instability (1 of 43) (1 cancer), 81% of unstable sporadic colorectal cancers (13 of 16), and none of the 61 stable or unstable gastric or esophageal cancers contained TGF-beta 1RII mutations.
  
  
  CONCLUSIONS
  Mutational inactivation of the poly A microsatellite tract within TGF-beta 1RII occurs early and in a subset of unstable UC neoplasms and commonly in sporadic colorectal cancers but may be rare in unstable gastric and esophageal tumors.
authors.affiliation: Department of Medicine, University of Maryland School of Medicine, Baltimore, USA.
authors.forename: R F
authors.initials: RF
authors.lastname: Souza
authors.forename: J
authors.initials: J
authors.lastname: Lei
authors.forename: J
authors.initials: J
authors.lastname: Yin
authors.forename: R
authors.initials: R
authors.lastname: Appel
authors.forename: T T
authors.initials: TT
authors.lastname: Zou
authors.forename: X
authors.initials: X
authors.lastname: Zhou
authors.forename: S
authors.initials: S
authors.lastname: Wang
authors.forename: M G
authors.initials: MG
authors.lastname: Rhyu
authors.forename: K
authors.initials: K
authors.lastname: Cymes
authors.forename: O
authors.initials: O
authors.lastname: Chan
authors.forename: W S
authors.initials: WS
authors.lastname: Park
authors.forename: M J
authors.initials: MJ
authors.lastname: Krasna
authors.forename: B D
authors.initials: BD
authors.lastname: Greenwald
authors.forename: J
authors.initials: J
authors.lastname: Cottrell
authors.forename: J M
authors.initials: JM
authors.lastname: Abraham
authors.forename: L
authors.initials: L
authors.lastname: Simms
authors.forename: B
authors.initials: B
authors.lastname: Leggett
authors.forename: J
authors.initials: J
authors.lastname: Young
authors.forename: N
authors.initials: N
authors.lastname: Harpaz
authors.forename: S J
authors.initials: SJ
authors.lastname: Meltzer
mesh_terms: D030201:Activin Receptors, Type I; D000230:Adenocarcinoma / Q000235:genetics*; D002277:Carcinoma / Q000235:genetics*; D003093:Colitis, Ulcerative / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000235:genetics*; D016147:Genes, Tumor Suppressor / Q000235:genetics; D006801:Humans; D018895:Microsatellite Repeats / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics*
chemical_list: D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I