EVIDENCE OF MULTISTEP ONCOGENESIS OF ORAL SQUAMOUS-CELL CARCINOMA

We examined biopsy samples from one oral cancer and three precancerous lesions of the tongue of an 81-year old woman by polymerase chain rea ction single-strand conformation polymorphism (PCR-SSCP) and sequence analyses using 18 oligonucleotide primer pairs of adenomatous polyposi s coli (APC) gene and 5 primers of p53 gene. Normal tongue epithelium adjacent to lesions was used as a control. The four lesions harbored t he common mutation of APC gene that was not detected in the control. A t codon 1621 in exon 15 of the APC gene there was a C to G substitutio n resulting in serine (TCA) to stop codon (TGA). No mutation of p53 ge ne was detected in any samples of the control and three precancerous l esions of the tongue. On the other hand, an A to G substitution at cod on 170 in exon 5 of p53 gene resulting in glutamic acid (ACG) to glyci ne (GCG) was detected in the DNA of her tongue cancer. These results m ay suggest that the four lesions have the same origin, and that multi- step oncogenesis had occurred, the APC gene alteration being one of th e early events in the process of tumorigenesis and p53 gene alteration involved in the late events.