LOSS OF P53 GENE AS A BIOMARKER OF HIGH-RISK ORAL LEUKOPLAKIAS

We have investigated loss of heterozygosity of p53 tumor suppressor ge ne in Indian oral cancer patients, individuals with premalignant leuko plakia lesions, and corresponding normal mucosa, to study the status o f p53 alleles in oral cancer pathogenesis. Fifty oral cancers, and 42 oral leukoplakia lesions and corresponding clinically normal oral muco sa from 18 individuals, were analysed. Peripheral blood cells (PBCs) f rom all the individuals and 47 normal healthy volunteers were also inc luded in the study. Polymerase chain reaction(PCR) of p53 Exon4, follo wed by restriction enzyme digestion with AccII due to the enzyme polym orphic site at Exon4 codon72, was used to detect homozygosity/heterozy gosity of p53 alleles, and compared with the allelic pattern in the co rresponding PBC. The PCR product subjected to AccII digestion detected 259bp, 160/99bp fragments indicating heterozygosity of p53 alleles in 69% of the 139 individuals. On comparison of the p53 allelic distribu tion in the lesions or tumour tissues, and corresponding PBC, LOH was observed in 20.5% oral tumors and 22% leukoplakias. However, there was no evidence of LOH in the clinically normal mucosa available from 16 individuals with leukoplakia. Our studies demonstrated LOH of p53 alle le in early and advanced stages of-oral cancers, as well as leukoplaki as, perhaps indicating p53 LOH as one of the early events in oral carc inogenesis. Thus, p53 LOH may be useful as a biomarker in defining a c ertain population of high risk leukoplakias that may progress to oral cancer.