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

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Author(s): Teresita Muñoz-Antonia | Mariclara Torrellas-Ruiz | Jonathan Clavell | Linda A. Mathews | Carlos A. Muro-Cacho | Adriana Báez

Journal: International Journal of Otolaryngology
ISSN 1687-9201

Volume: 2009;
Date: 2009;
Original page

ABSTRACT
Background. Alterations in TGF-β signaling are common in head and neck cancer (HNSCC). Mutations in TGF-β type II receptor (TβR-II) occur frequently in HNSCC while TGF-β type I receptor (TβR-I) mutations are rare, suggesting that other molecular alterations in the TGF-β pathway are likely. To identify abnormalities in TβR-I expression we analyzed 50 HNSCCs and correlated the results with clinical-pathologic features. Methods. Hypermethylation of TβR-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. TβR-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 TβR-I expression in HNSCC is associated with DNA hypermethylation.
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