title: Aberrant methylation inactivates transforming growth factor Beta receptor I in head and neck squamous cell carcinoma.
abstract: Background. Alterations in TGF-beta signaling are common in head and neck cancer (HNSCC). Mutations in TGF-beta type II receptor (TbetaR-II) occur frequently in HNSCC while TGF-beta type I receptor (TbetaR-I) mutations are rare, suggesting that other molecular alterations in the TGF-beta pathway are likely. To identify abnormalities in TbetaR-I expression we analyzed 50 HNSCCs and correlated the results with clinical-pathologic features. Methods. Hypermethylation of TbetaR-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. TbetaR-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 TbetaR-I expression in HNSCC is associated with DNA hypermethylation.
authors.affiliation: Department of Interdisciplinary Oncology, Moffitt Cancer Center, Tampa, FL 33612, USA.
authors.forename: Teresita
authors.initials: T
authors.lastname: Muñoz-Antonia
authors.forename: Mariclara
authors.initials: M
authors.lastname: Torrellas-Ruiz
authors.forename: Jonathan
authors.initials: J
authors.lastname: Clavell
authors.forename: Linda A
authors.initials: LA
authors.lastname: Mathews
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Muro-Cacho
authors.forename: Adriana
authors.initials: A
authors.lastname: Báez