Mutation of p53 Gene and Detection of Human Papillomavirus DNA in Larynx and Pharynx Cancers

Park, Young Hak; Jo, Seung Ho

Abstract

Mutations in the p53 tumor suppressor gene have been shown to be one of the most common genetic abnormalities in human cancers. Loss of p53 tumor suppressor gene function can occur through gene mutation or interaction with early proteins of oncogenic viruses such as E6 protein of human papillomaviruses(HPV). We studied 24 squamous cell carcinomas of the larynx(20) and hypopharynx(4) for p53 gene mutations as well as for the presence of oncogenic HPV DNA. Exon 5 through 8 of the p53 gene were examined using polymerase chain reaction-direct sequencing methods. HPV detection was done using polymerase chain reaction amplification with HPV L1 consensus primer. HPV type was determined by the same method using HPV-16 and -18 type-specific E6 primers. The results were as follows: 1) Eight of 24 tumors(33%) had p53 mutations, one of which had 2 mutational sites. All cases of which had p53 mutations or HPV DNA detection were larynx cancer. 2) p53 genetic alteration in larynx cancer included seven missense mutations resulting in single amino acid substitutions, one nonsense mutation encoding a stop codon and one silent mutation. Six of 9(66.7%) mutations occurred in two distinct regions of the genes, codon 245-248(3 mutations) and codon 283-294(3 mutations). 3) The p53 mutational spectrum observed was characterized by G to T transversion(4 of 9), T to A transversion(2 of 9), C to A transversion(1 of 9), G to A transition(1 of 9) and C to T transition(1 of 9). 4) HPV DNA was detected in 3 of 24(12.5%) tumors. According to the type of HPV DNA, HPV-16 was detected in 1 case and HPV non-16, -18 was detected in 2 cases, one of which had p53 mutation. 5) There was no relationship between p53 mutations or HPV DNA detection and clinicopathologic parameters. These results suggest that p53 mutations may play an important role in carcinogenesis of laryngeal cancer. Further study is necessary to clarify the role of p53 mutation and oncogenic HPV infection on clinical outcome of laryngeal cancer.