비인두 암종에서 Epstein-Barr virus 감염과 p53 유전자 변이의 관계
A Relationship of Epstein-Barr Virus with p53 Mutation in Nasopharyngeal Carcinoma
구강과학- 전남대학교 2001년 13권 1호 p.79 ~ 91
박영식, 최홍란,
소속 상세정보
박영식 ( ) - 전남대학교 치과대학 구강병리학교실
최홍란 ( ) - 전남대학교 치과대학 구강병리학교실
KMID : 0988420010130010079
Abstract
Nasopharyngeal carcinoma is a common neoplasm of the head and neck, and commonly found in Southeast Asia. Epstein Barr virus(EBV) is found within the malignant cells in most cases of nasopharyngeal carcinoma. The p53 gene has been implicated as a tumor suppressing gene in many types of human cancers, but the frequency of mutations varies in different cancers.
To find out the correlation between EBV infection and p53 mutation in nasopharyngeal carcinoma, we evaluated the presence of EBV using EBER 1 in situ hybridization and a mutation of p53, using PCR SSCP analysis and DAN sequencing method.
We examined nasopharyngeal specimens from 33 patients, histologicaly consisting of 27 cases of nonkeratinizing squamous cell carcinoma (WHO Ⅱ) and 6 cases of undifferentiated carcinoma (WHO Ⅲ) according to the World Health Organization claasification. EBER1 were detected in 14 of 33 (42.4%) cases. Positive hybridization signals were restricted to the nuclei of tumor cells. Of 14 cases 14 cases, 11 out of 27 (40.7%) cases of WHO Ⅱ, and 3 out 6 (50%) cases of WHO Ⅲ were positive.
33 biopsy specimens were analyzed by PCR SSCP for p53 gene mutations. Our study concentrated on exons 5 through 9 of the p53 gene. However, we did not detect any mobility shifts n exon 5/6, 7 and 8/9 of the p5 gene in comparison to the banding patterns of the normal control.
The reliability of the SSCP analysis was confirmed by sequencing five randomly chosen specimens for the exon 5 9 region. Among five cases, 4 out 5 cases were EBER1 positive and histologially WHO Ⅱ, and 1 out of 5 cases were EBER1 negative and WHO Ⅲ. We detected point mutation in 3 cases were EBER 1 positive and WHO Ⅱ. No alteration of the exon 7 and 8/9 of the p53 sequence was observed. Alteration occurred in 2 out of 3 cases; GCC was replaced by GTC at codon 131, resulting in a change in amino acid sequence from alanine to valine. In one 3 cases, TCC was replaced by TTC at codon 149, resulting in a change from arginine to arginine.
Based on the above results, this study shows correlation between the presence of EBV and mutations of the p53 gene, suggesting contributions to malignant transformation in nasopharynx. We need to futher investigate this situation to understand the stepwise progression of nasopharyngeal carcinogenesis.
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