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.

R. F. Souza, L. Garrigue-Antar, J. Lei, J. Yin, R. Appel, V. F. Vellucci, T. T. Zou, X. Zhou, S. Wang, M. G. Rhyu, K. Cymes, O. Chan, W. S. Park, M. J. Krasna, B. D. Greenwald, J. Cottrell, J. M. Abraham, L. Simms, B. Leggett, J. YoungN. Harpaz, M. Reiss, S. J. Meltzer

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

BACKGROUND & AIMS: 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.

Original languageEnglish (US)
Pages (from-to)229-236
Number of pages8
JournalHuman cell : official journal of Human Cell Research Society
Volume9
Issue number3
StatePublished - Sep 1996

ASJC Scopus subject areas

  • Cell Biology
  • Cancer Research

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    Souza, R. F., Garrigue-Antar, L., Lei, J., Yin, J., Appel, R., Vellucci, V. F., Zou, T. T., Zhou, X., Wang, S., Rhyu, M. G., Cymes, K., Chan, O., Park, W. S., Krasna, M. J., Greenwald, B. D., Cottrell, J., Abraham, J. M., Simms, L., Leggett, B., ... Meltzer, S. J. (1996). 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. Human cell : official journal of Human Cell Research Society, 9(3), 229-236.