Transforming growth factor-beta receptor type I gene is frequently mutated in ovarian carcinomas.
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| Abstract |
Ovarian carcinomas (OCs), particularly recurrent OCs, are frequently resistant to transforming growth factor (TGF)-beta-mediated growth inhibition. Mutations in the TGF-beta receptor type II (TbetaR-II) gene are only evident in a minority of OCs, suggesting that other alterations of the TGF-beta 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-beta receptor I (TbetaR-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 TbetaR-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 TbetaR-I is frequently mutated in OC and suggest that resistance to TGF-beta-mediated growth inhibition may frequently involve alterations of the TbetaR-I gene.
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| Authors | T Chen, J Triplett, B Dehner, B Hurst, B Colligan, J Pemberton, J R Graff, J H Carter |
| Journal | Cancer research (Cancer Res) Vol. 61 Issue 12 Pg. 4679-82 (Jun 15 2001) ISSN: 0008-5472 [Print] United States |
| PMID | 11406536 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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