Down-regulation of FEZ1/LZTS1 gene with frequent loss of heterozygosity in oral squamous cell carcinomas.

Allelic deletions on the short arm of chromosome 8 (8p) are frequent events in several human malignancies, including oral cancer. We have examined and found two common regions of deletion on 8p (8p12, 8p22) in oral squamous cell carcinomas (SCC)s. The possible involvement of FEZ1/LZTS1 (FEZ1) gene, a candidate tumor suppressor gene, mapped at 8p22, was also evaluated. Here we analyzed whether FEZ1 alterations play a role in the development and progression of oral SCCs. In the present study, we examined FEZ1 expression in 31 primary oral SCCs and 8 SCC-derived cell lines by reverse transcription-PCR (RT-PCR). Thirty-five percent of tumors (11 of 31) and 100% of cell lines (8 of 8) showed absent or reduced mRNA gene expression. To investigate the mechanism for silencing, cells were cultured with 5-aza-2'-deoxycytidine and all the cell lines showed restoration by the demethylating agent. These findings suggest that inactivation of the FEZ1 gene may contribute to the development of oral SCCs.