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International Journal of Otolaryngology
Volume 2009 (2009), Article ID 848695, 10 pages
Research Article

Aberrant Methylation Inactivates Transforming Growth Factor Receptor I in Head and Neck Squamous Cell Carcinoma

1Department of Interdisciplinary Oncology, Moffitt Cancer Center, Tampa, FL 33612, USA
2Department of Pathology, LSU Health Sciences Center, New Orleans, LA 70112, USA
3Department of Pharmacology, University of Puerto Rico School of Medicine, San Juan, PR 00936, USA
4Pathology and Laboratory Medicine, James A. Haley Veterans' Affairs Medical Center, Tampa, FL 33612, USA
5Department of Otolaryngology, University of Puerto Rico School of Medicine, San Juan, PR 00936, USA

Received 10 December 2008; Accepted 27 March 2009

Academic Editor: Alfio Ferlito

Copyright © 2009 Teresita Muñoz-Antonia et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Background. Alterations in TGF- signaling are common in head and neck cancer (HNSCC). Mutations in TGF- type II receptor (T R-II) occur frequently in HNSCC while TGF- type I receptor (T R-I) mutations are rare, suggesting that other molecular alterations in the TGF- pathway are likely. To identify abnormalities in T R-I expression we analyzed 50 HNSCCs and correlated the results with clinical-pathologic features. Methods. Hypermethylation of T R-I was evaluated via methylation-specific PCR (MSP) and restriction enzyme-mediated PCR (MSRE). Mutations in exons 1 and 7, mRNA and protein expression were analyzed by direct sequencing, semiquantitative RT—PCR and immunohistochemistry, respectively. Results. T R-I expression was lost in 83% HNSCCs and was linked to DNA hypermethylation of the CpG-rich promoter region in 62% of the tumors. The variants 9A/6A and Int7G24A were found in two patients. Conclusions. This study shows that suppression of T R-I expression in HNSCC is associated with DNA hypermethylation.