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Oral squamous cell carcinoma (OSCC) is the 3rd leading malignancy in the male population of developing countries. In South Asians, OSCC is tightly linked to areca chewing. Since the prognosis for OSCC remains dismal, improvement of early diagnosis may benefit the survival of victims. Chromosome region 3q26-27 has been shown to carry several oncogenes and is a hot-spot region for genomic alterations in squamous cell carcinoma. By quantitative polymerase chain reaction (PCR), we have determined the gene copy number (CN) of TERC (3q26.2), PI3KCA (3q26.32), ZASC1 (3q26.33), and TP63 (3q27.2) from microdissected OSCC. Our results showed that CN amplifications of PI3KCA and ZASC1, a newly identified zinc finger transcription factor, were the most prominent alterations in primary and metastatic OSCC. Co-amplification of PI3KCA and ZASC1 in 50% of primary OSCC suggested that they are critical targets of 3q26.3 amplicon. In addition, OSCC carrying the higher PI3KCA and/or ZASC1 CN amplification conferred significantly higher propensity for lymph node metastasis than the counterparts. Quantitative-reverse transcription-PCR analysis also indicated that the great increase in ZASC1 mRNA expression in OSCC is associated with lymph node metastasis. We further detected the lower CN amplification of 3q26-27 oncogenes (2-5 folds CN increase) in brushed samples from oral leukoplakia, validating the sensitivity of this assay. In addition to OSCC, CN amplification of any of the four 3q26-27 oncogenes was also detected in the brushed samples from 20% areca chewers without visible lesion. The frequent CN amplification of TERC in oral leukoplakia and areca chewers suggested that it could be an early event in oral carcinogenesis. In summary, our data indicated the CN amplification and overexpression of ZASC1 in OSCC. The findings also suggested the potential on using the combination of quantitative-PCR on brush sampling to dissect OSCC risk population, and close follow-up has been performed to warrant the neoplastic formation. Key words: amplification, areca, quantitative-PCR, oncogene, oral carcinoma

[Proc Amer Assoc Cancer Res, Volume 46, 2005]