Cancer Research CTRC-AACR San Antonio Breast Cancer Symposium Translational Medicine Conference in Israel
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Chen, T.
Right arrow Articles by Carter, J. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chen, T.
Right arrow Articles by Carter, J. H.
[Cancer Research 61, 4679-4682, June 15, 2001]
© 2001 American Association for Cancer Research

Advances in Brief

Transforming Growth Factor-ß Receptor Type I Gene Is Frequently Mutated in Ovarian Carcinomas1

Taiping Chen2, Jason Triplett, Ben Dehner, Bernadette Hurst, Bruce Colligan, Jackson Pemberton, Jeremy R. Graff and Julia H. Carter

Wood Hudson Cancer Research Laboratory, Newport, KY 41071-4701 [T. C., J. T., B. D., B. H., B. C., J. H. C.]; Department of Pathology and Laboratory Medicine, St. Elizabeth Medical Center, Edgewood, KY 41017 [J. P.]; and Lilly Research Laboratory, Cancer Research Division, Eli Lilly and Company, Indianapolis, Indiana 46285 [J. R. G.]

Ovarian carcinomas (OCs), particularly recurrent OCs, are frequently resistant to transforming growth factor (TGF)-ß-mediated growth inhibition. Mutations in the TGF-ß receptor type II (TßR-II) gene are only evident in a minority of OCs, suggesting that other alterations of the TGF-ß signaling pathway may be involved in OC. Using PCR, cold single-strand conformation polymorphism, and DNA sequencing, we now show that 33% of primary OCs (10 of 30) harbor somatic changes in exons 2, 3, 4, and 6 of the TGF-ß receptor I (TßR-I) gene. Most of the changes are missense mutations and clustered largely in the catalytic domain of the receptor kinase. Interestingly, seven additional cases (23.3%) showed heterozygous carriers of an allelic variant [a 9-nucleotide deletion, del(GGC)3] in exon 1 of the TßR-I gene. This is in contrast with 10.6% of del(GGC)3 heterozygous carriers in a recent report of a large normal population (n = 735; B. Pasche et al., Cancer Res., 59: 5678–5682, 1999). These results indicate that TßR-I is frequently mutated in OC and suggest that resistance to TGF-ß-mediated growth inhibition may frequently involve alterations of the TßR-I gene.




This article has been cited by other articles:


Home page
 Cancer Res.Home page
J. S. Sunde, H. Donninger, K. Wu, M. E. Johnson, R. G. Pestell, G. S. Rose, S. C. Mok, J. Brady, T. Bonome, and M. J. Birrer
Expression Profiling Identifies Altered Expression of Genes That Contribute to the Inhibition of Transforming Growth Factor-{beta} Signaling in Ovarian Cancer.
Cancer Res., September 1, 2006; 66(17): 8404 - 8412.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
J.-H. Mao, E. F. Saunier, J. P. de Koning, M. M. McKinnon, M. N. Higgins, K. Nicklas, H.-T. Yang, A. Balmain, and R. J. Akhurst
Genetic variants of Tgfb1 act as context-dependent modifiers of mouse skin tumor susceptibility
PNAS, May 23, 2006; 103(21): 8125 - 8130.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
T. Chen, C. R. Jackson, A. Link, M. P. Markey, B. M. Colligan, L. E. Douglass, J. O. Pemberton, J. A. Deddens, J. R. Graff, and J. H. Carter
Int7G24A Variant of Transforming Growth Factor-{beta} Receptor Type I Is Associated with Invasive Breast Cancer
Clin. Cancer Res., January 15, 2006; 12(2): 392 - 397.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
H.-T. Zhang, J. Zhao, S.-Y. Zheng, and X.-F. Chen
Is TGFBR1*6A Really Associated With Increased Risk of Cancer?
J. Clin. Oncol., October 20, 2005; 23(30): 7743 - 7744.
[Full Text] [PDF]

Home page
 JAMAHome page
B. Pasche, T. J. Knobloch, Y. Bian, J. Liu, S. Phukan, D. Rosman, V. Kaklamani, L. Baddi, F. S. Siddiqui, W. Frankel, et al.
Somatic Acquisition and Signaling of TGFBR1*6A in Cancer
JAMA, October 5, 2005; 294(13): 1634 - 1646.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
Q. Zhang, J. N. Rubenstein, T. L. Jang, M. Pins, B. Javonovic, X. Yang, S.-J. Kim, I. Park, and C. Lee
Insensitivity to Transforming Growth Factor-{beta} Results from Promoter Methylation of Cognate Receptors in Human Prostate Cancer Cells (LNCaP)
Mol. Endocrinol., September 1, 2005; 19(9): 2390 - 2399.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
W. Ding, Q. Tang, V. Espina, L. A. Liotta, D. T. Mauger, and K. M. Mulder
A Transforming Growth Factor-{beta} Receptor-Interacting Protein Frequently Mutated in Human Ovarian Cancer
Cancer Res., August 1, 2005; 65(15): 6526 - 6533.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
Y. Bian, T. Caldes, J. Wijnen, P. Franken, H. Vasen, V. Kaklamani, K. Nafa, P. Peterlongo, N. Ellis, J. A. Baron, et al.
TGFBR1{star}6A May Contribute to Hereditary Colorectal Cancer
J. Clin. Oncol., May 1, 2005; 23(13): 3074 - 3078.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. Ammanamanchi and M. G. Brattain
Restoration of Transforming Growth Factor-{beta} Signaling through Receptor RI Induction by Histone Deacetylase Activity Inhibition in Breast Cancer Cells
J. Biol. Chem., July 30, 2004; 279(31): 32620 - 32625.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. C. Dowdy, A. Mariani, and R. Janknecht
HER2/Neu- and TAK1-mediated Up-regulation of the Transforming Growth Factor {beta} Inhibitor Smad7 via the ETS Protein ER81
J. Biol. Chem., November 7, 2003; 278(45): 44377 - 44384.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
V. G. Kaklamani, N. Hou, Y. Bian, J. Reich, K. Offit, L. S. Michel, W.S. Rubinstein, A. Rademaker, and B. Pasche
TGFBR1*6A and Cancer Risk: A Meta-Analysis of Seven Case-Control Studies
J. Clin. Oncol., September 1, 2003; 21(17): 3236 - 3243.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
T. V. Parekh, P. Gama, X. Wen, R. Demopoulos, J. S. Munger, M.-L. Carcangiu, M. Reiss, and L. I. Gold
Transforming Growth Factor {beta} Signaling Is Disabled Early in Human Endometrial Carcinogenesis Concomitant with Loss of Growth Inhibition
Cancer Res., May 1, 2002; 62(10): 2778 - 2790.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
L. D. Dunfield, E. J. C. Dwyer, and M. W. Nachtigal
TGF{beta}-Induced Smad Signaling Remains Intact in Primary Human Ovarian Cancer Cells
Endocrinology, April 1, 2002; 143(4): 1174 - 1181.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
A.-M. Stefanovska, G. D. Efremov, A. J. Dimovski, D. Jasar, G. Zografski, T. Josifovski, M. Panovski, R. Jankova, M. Spiroski, B. Pasche, et al.
T{beta}R-I(6A) Polymorphism Is not a Tumor Susceptibility Allele in Macedonian Colorectal Cancer Patients Correspondence re: B. Pasche et al. Type I T{beta}R-I(6A) Is a Candidate Tumor Susceptibility Allele. Cancer Res., 58: 2727-2732, 1998.
Cancer Res., November 1, 2001; 61(22): 8351 - 8351.
[Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2001 by the American Association for Cancer Research.