ABNORMALITIES OF THE ADENOMATOUS POLYPOSIS-COLI GENE IN HUMAN ORAL SQUAMOUS-CELL CARCINOMA

Recent studies have suggested that abnormalities in the adenomatous po lyposis coli gene (APC gene) are associated with the development not o nly of familial adenomatous polyposis coli (FAP) but also of cancers i n digestive organs. In order to elucidate whether abnormalities of the APC gene could contribute to the development of oral squamous-cell ca rcinoma (SCC), genomic DNAs from tumors and normal tissues of 24 unrel ated Japanese patients were examined by using PCR-SSCP (polymerase cha in reaction single-strand conformation polymorphism) and sequence anal yses. Five novel nucleotide substitutions of the APC gene in tumor tis sues were identified in 3 patients with oral SCC (12.5%), resulting in 3 amino-acid replacements or a truncation of the APC gene product. We also examined 24 tumor and 24 normal tissue samples for loss of heter ozygosity (LOH) at exon 11 of the APC gene by PCR-LOH assay. In this a nalysis, 45.8% of samples were informative and LOH was detected in 72. 7% of informative cases. The frequency of LOH in oral SCC was similar to that previously reported in esophageal SCC. These results suggest t hat abnormalities in the APC gene are associated with the development of human oral SCC. (C) 1994 Wiley-Liss, Inc.