Aberrant methylation inactivates transforming growth factor Beta receptor I in head and neck squamous cell carcinoma.
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.
Muñoz-Antonia
Teresita
T
Department of Interdisciplinary Oncology, Moffitt Cancer Center, Tampa, FL 33612, USA.
Torrellas-Ruiz
Mariclara
M
Clavell
Jonathan
J
Mathews
Linda A
LA
Muro-Cacho
Carlos A
CA
Báez
Adriana
A