SYNCHRONOUS ORAL CARCINOMAS - INDEPENDENT OR COMMON CLONAL ORIGIN

Second primary tumors in patients with head and neck cancer have a det rimental impact on long-term survival; at least 15% of patients develo p additional tumors. Originally, it was hypothesized that multiple tum ors developed independently after widespread epithelial exposure to ca rcinogens (the field cancerization theory), but recent molecular studi es now support the alternative theory of a common clonal origin. If mu ltiple tumors originate from the same clone, early genetic alterations in these cells should be common to all of the tumors. We have compare d the pattern of allelic imbalance in paired tumors from five male pat ients with two synchronous oral squamous cell carcinomas and in periph eral dysplasia using microsatellite markers on chromosomes 3p, 9p, and 17p. Discordance, usually through loss of alternate alleles at the sa me microsatellite loci, was detected in two patients. The remaining th ree patients had identical alterations in their tumors. The changes id entified occurred early in tumorigenesis, because, with only one excep tion, these were also present in the associated dysplasia. Thus, we pr ovide evidence that synchronous oral squamous cell carcinomas are of i ndependent origin in some patients but may be of common clonal origin in others.