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

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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

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Microsatellite Instability
Ulcerative Colitis
Transforming Growth Factor beta
Stomach Neoplasms
Colorectal Neoplasms
Carcinoma
Neoplasms
Mutation
Microsatellite Repeats
transforming growth factor-beta type II receptor
Polymerase Chain Reaction
Messenger RNA
Stomach
Gene Silencing
Carcinogenesis

ASJC Scopus subject areas

  • Cell Biology
  • Cancer Research

Cite this

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. / 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.; Young, J.; Harpaz, N.; Reiss, M.; Meltzer, S. J.

In: Human cell : official journal of Human Cell Research Society, Vol. 9, No. 3, 09.1996, p. 229-236.

Research output: Contribution to journalArticle

Souza, RF, Garrigue-Antar, L, Lei, J, Yin, J, Appel, R, Vellucci, VF, Zou, TT, Zhou, X, Wang, S, Rhyu, MG, Cymes, K, Chan, O, Park, WS, Krasna, MJ, Greenwald, BD, Cottrell, J, Abraham, JM, Simms, L, Leggett, B, Young, J, Harpaz, N, Reiss, M & Meltzer, SJ 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, vol. 9, no. 3, pp. 229-236.
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. ; Young, J. ; Harpaz, N. ; Reiss, M. ; Meltzer, S. J. / 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. In: Human cell : official journal of Human Cell Research Society. 1996 ; Vol. 9, No. 3. pp. 229-236.
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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 = "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.",
author = "Souza, {R. F.} and L. Garrigue-Antar and J. Lei and J. Yin and R. Appel and Vellucci, {V. F.} and Zou, {T. T.} and X. Zhou and S. Wang and Rhyu, {M. G.} and K. Cymes and O. Chan and Park, {W. S.} and Krasna, {M. J.} and Greenwald, {B. D.} and J. Cottrell and Abraham, {J. M.} and L. Simms and B. Leggett and J. Young and N. Harpaz and M. Reiss and Meltzer, {S. J.}",
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T1 - 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.

AU - Souza, R. F.

AU - Garrigue-Antar, L.

AU - Lei, J.

AU - Yin, J.

AU - Appel, R.

AU - Vellucci, V. F.

AU - Zou, T. T.

AU - Zhou, X.

AU - Wang, S.

AU - Rhyu, M. G.

AU - Cymes, K.

AU - Chan, O.

AU - Park, W. S.

AU - Krasna, M. J.

AU - Greenwald, B. D.

AU - Cottrell, J.

AU - Abraham, J. M.

AU - Simms, L.

AU - Leggett, B.

AU - Young, J.

AU - Harpaz, N.

AU - Reiss, M.

AU - Meltzer, S. J.

PY - 1996/9

Y1 - 1996/9

N2 - 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.

AB - 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.

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