title: Alterations of transforming growth factor-beta 1 receptor type II occur in ulcerative colitis-associated carcinomas, sporadic colorectal neoplasms, and esophageal carcinomas, but not in gastric neoplasms.
abstract: OBJECTIVE
  Gastric cancers, sporadic colorectal cancers, and ulcerative colitis (UC)-associated colorectal carcinomas and dysplasias manifest microsatellite instability (MI); however, esophageal carcinomas rarely exhibit MI. Recently, a transforming growth factor-beta 1 type II receptor (TGF-beta 1RII) mutation in a coding microsatellite was described in primary colorectal carcinomas demonstrating MI. No previous studies of TGF-beta 1RII have addressed mechanisms of inactivation other than MI in human tumors; furthermore, MI-negative tumors have not been examined for TGF-beta 1RII mutation. We evaluated 138 primary human neoplasms for mutation in the poly-A microsatellite tract of TGF-beta 1RII. Additionally, a group of esophageal tumors was evaluated for the expression of TGF-beta 1RII messenger RNA (mRNA).
  
  
  METHODS
  First, we determined whether MI was present at other chromosomal loci in these lesions. The poly-deoxyadenine (poly-A) microsatellite tract within the TGF-beta 1RII coding region was then PCR-amplified. In a group of MI-negative esophageal tumors, RT-PCR was performed to determine the expression of TGF-beta 1RII mRNA.
  
  
  RESULTS
  Among 17 MI+ UC specimens, 3 (18%) demonstrated TGF-beta 1RII poly-A tract mutation (2 cancers and 1 dysplasia), while 2 (4%) of 44 MI-negative UC specimens (1 dysplasia and 1 tumor), and 13 (81%) of 16 MI+ sporadic colorectal cancers, contained TGF-beta 1RII poly-A mutation. No gastric or esophageal tumors contained TGF-beta 1RII mutation. Among 21 MI-negative esophageal carcinomas. 6 cases (28.5%) had TGF-beta 1RII transcripts that were low or undetectable by RT-PCR.
  
  
  CONCLUSIONS
  Mutation within the poly-A microsatellite tract of TGF-beta 1RII occurs early in a subset of UC-neoplasms and commonly in sporadic colorectal cancers, but may be rare in MI+ gastric tumors. Diminished expression of TGF-beta 1RII mRNA in esophageal tumors suggests that mechanisms of inactivation in this gene other than MI play a role in esophageal carcinogenesis.
authors.affiliation: Department of Medicine (GI Division), University of Maryland School of Medicine, USA.
authors.forename: R F
authors.initials: RF
authors.lastname: Souza
authors.forename: L
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authors.lastname: Garrigue-Antar
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: V F
authors.initials: VF
authors.lastname: Vellucci
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
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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
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authors.initials: M
authors.lastname: Reiss
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authors.initials: SJ
authors.lastname: Meltzer
mesh_terms: D003093:Colitis, Ulcerative / Q000150:complications*; D015179:Colorectal Neoplasms / Q000209:etiology / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000235:genetics*; D006801:Humans; D018895:Microsatellite Repeats; D009154:Mutation; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger / Q000032:analysis; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II