MUTATIONS OF KI-RAS ONCOGENE CODON-12 IN BETEL QUID CHEWING-RELATED HUMAN ORAL SQUAMOUS-CELL CARCINOMA IN TAIWAN

In Taiwan, there are two million people who have a betel quid chewing habit, and approximately 80% of all oral cancer deaths are associated with this habit. To investigate the incidence and types of Ki-rus codo n 12 mutations in oral cancer associated with betel quid chewing, we u sed a sensitive mutation-specific two-stage polymerase chain reaction (PCR) technique to examine human oral squamous cell carcinomas from fo rmalin-fixed, paraffin-embedded tissues. DNA sequence analysis of PCR products revealed that 6 of 33 (18%) tumour specimens contained Ki-ras codon 12 mutations. Four of the tumours contained more than one mutat ion. Three different base changes were detected, resulting from a subs titution of wild type glycine (GGT) to either serine (AGT), aspartic a cid (GAT) or cysteine (TAT). These results indicate that Ki-ras oncoge ne activation may play a role in the oncogenesis of betel quid chewing -related human oral squamous cell carcinomas.