Tumor suppressor gene (TSG) has a very important role in cancer formation and squamous cell carcinoma (SCC) is the most common malignant tumor in oral region. So the aim of our study is a finding a new TSG in oral SCC.
Loss of Heterozygosity (LOH) is an effective means to discover TSG. In past studies, LOH has been frequently detected at chromosome 4q22-35 region in human oral SCC. This suggests the existence of tumor suppressor genes.
We analysed LOH at 4q22-35 region in 40 oral SCC casrs by using 17 microsatellite markers and found allelic deletions in 85% (34/40) of the significant cases. We detected two high LOH regions, one is around D4S2623 and the other is around D4S1644. D4S2623 showed the higher LOH frequency being 44%.
When we redefined the map of 4q22-35 region according to the contiguous sequences, we observed gene Caspase-6 in the proximity of D4S2623, which has a relevant function during apoptosis and therefore can also work like TSG.

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In our past study, we confirmed the highest Loss of heterozygosity frequency in 4q25 (D4S2623), and we observed gene Caspase-6 in the proximity to D4S2623, which has a relevant function during apoptosis and therefore can also work like TSG.
So we examined Caspase-6 mRNA expression level. Reverse-transcription-PCR analysis demonstrated decreased expression in 40% and equal expression in 30% of Caspase-6 mRNA of primary tumors as compared with the matched normal samples.
We also examined Caspase-6 cDNA sequencing for mutations. But no mutation was detected.
These findings suggested the possibility of Caspase-6 gene to function as a tumor suppressor gene in a subset of oral SCC.

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