The p16(INK4 alpha)/p19(ARF) gene mutations are infrequent and are mutually exclusive to p53 mutations in Indian oral squamous cell carcinomas

Eighty-seven untreated primary oral squamous cell carcinomas (SCCs) associa ted with betel quid and tobacco chewing from Indian patients were analysed for the presence of mutations in the commonly shared exon 2 of p16(INK4 alp ha)/p19(ARF) genes. Polymerase chain reaction-single strand conformation po lymorphism (PCR-SSCP) and sequencing analysis were used to detect mutations . SSCP analysis indicated that only 9% (8/87) of the rumours had mutation i n p16(INK4 alpha)/p19(ARF) genes. Seventy-two rumours studied here were pre viously analysed for p53 mutations and 21% (15/72) of them were found to ha ve mutations in p53 gene. Only one tumour was found to have mutation at bot h p53 and p16(INK4 alpha)/p19(ARF) genes. Thus, the mutation rates observed were 21% for p53, 9% for p16(INK4 alpha)/p19(ARF), and 1% for both. Sequen cing analysis revealed two types of mutations; i) G to C (GCAG to CCAG) tra nsversion type mutation at intron 1-exon 2 splice junction and ii) another C to T transition type mutation resulting in CGA to TGA changing arginine t o a termination codon at p16(INK4 alpha) gene codon 80 and the same mutatio n will alter codon 94 of p10(ARF) gene from CCG to CTG (proline to leucine) . These results suggest that p16(INK4 alpha)/p19(ARF) mutations are less fr equent than p53 mutations in Indian oral SCCs. The p53 and p16(INK4 alpha)/ p19(ARF) mutational events are independent and are mutually exclusive sugge sting that mutational inactivation of either p53 or p16(INK4 alpha)/p19(ARF ) may alleviate the need for the inactivation of the ether gene.