Mutational state of tumor suppressor genes (DCC, DPC4) and alteration on chromosome 18q21 in human oral cancer

Abstract

In order to investigate the roles of two candidate tumor suppressor genes, DCC (deleted in colorectal carcinoma) and DPC4 (deleted in pancreatic carcinoma 4) genes in oral squamous cell carcinoma (SCC), we examined 32 primary SCCs by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis. Additionally, 32 pairs of normal and tumor DNA from 32 patients with oral SCCs were also analyzed for loss of heterozygosity (LOH) using 10 microsatellite markers on chromosome 18q21 where DCC and DPC4 genes are localized. We detected point mutations of DPC4 gene in two cases by PCR-SSCP analysis and sequencing. One case showed an AGC (Ser) to ACC (Thr) missense mutation at codon 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 frequency (33.3%) of LOH was found at D18S46, and this was significantly correlated with the pathological results. These findings suggest that DCC and DPC4 gene may play minor roles in the genesis of oral SCC, and that another tumor suppressor gene involved in the development of oral SCC may exist in the region of D18S46 of this chromosome.