FREQUENT MUTATION OF P16 IN SQUAMOUS-CELL CARCINOMA OF THE HEAD AND NECK

RNA was isolated from 22 squamous cell carcinomas (SCCs) obtained from diverse sites within the head and neck and from matched normal tissue where available. Tissue samples were then screened for expression of RNA from tumor suppressor gene p16 by utilizing semiquantitative rever se transcriptase polymerase chain reaction (RT-PCR) analysis. p16-Spec ific PCR amplification products generated from tumor samples were subj ect to further analysis by direct DNA sequencing to determine if any t umor sample harbored a p16 mutation. The results show the presence of mutations in 10 of 22 (45%) of the tumor samples. Mutations comprise t wo identical point mutations, two small deletions (1 bp and 2 bp), one single-nucleotide insertion, four larger deletions, and an insertion/ deletion. No mutations in p16 have been identified by analysis of PCR products generated from normal matched tissue, suggesting that p16 alt erations are generated by somatic mutation and are not germline in ori gin. All 22 samples were analyzed additionally by immunohistochemistry for nuclear expression of the retinoblastoma (RB) tumor suppressor ge ne product. Results show lack of RE nuclear expression in only one sam ple, suggesting that mutation of RE is an infrequent event in the deve lopment of SCC of the head and neck (SCCHN).