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

[摘要] Background. Alterations in TGF-βsignaling are common in head and neck cancer (HNSCC). Mutations in TGF-βtype II receptor (TβR-II) occur frequently in HNSCC while TGF-βtype I receptor (TβR-I) mutations are rare, suggesting that other molecular alterations in the TGF-βpathway are likely. To identify abnormalities inTβR-Iexpression we analyzed 50 HNSCCs and correlated the results with clinical-pathologic features.Methods. Hypermethylation ofTβR-Iwas 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-Iexpression 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 ofTβR-Iexpression in HNSCC is associated with DNA hypermethylation.

[学科分类] 耳鼻喉科学