MUTATIONAL STATE OF TUMOR-SUPPRESSOR GENES (DCC, DPC4) AND ALTERATIONON CHROMOSOME 18Q21 IN HUMAN ORAL-CANCER

In order to investigate the roles of two candidate tumor suppressor ge nes, DCC (deleted in colorectal carcinoma) and DPC4 (deleted in pancre atic carcinoma 4) genes in oral squamous cell carcinoma (SCC), we exam ined 32 primary SCCs by polymerase chain reaction-single strand confor mation polymorphism (PCR-SSCP) analysis. Additionally, 32 pairs of nor mal and tumor DNA from 32 patients with oral SCCs were also analyzed f or loss of heterozygosity (LOH) using 10 microsatellite markers on chr omosome 18q21 where DCC and DPC4 genes are localized. We detected poin t mutations of DPC4 gene in two cases by PCR-SSCP analysis and sequenc ing. One case showed an AGC (Ser) to ACC (Thr) missense mutation at co don 1061 and the other the substitution C for A of the intron between exons 7 and 8. No mutation of DCC gene was observed in our cases. LOH at 18q21 was observed in 14 of the 32 cases (43.8%). The highest frequ ency (33.3%) of LOH was found at D18S46, and this was significantly co rrelated with the pathological results. These findings suggest that DC C and DPC4 gene may play minor roles in the genesis of oral SCC, and t hat another tumor suppressor gene involved in the development of oral SCC may exist in the region of D18S46 of this chromosome.