Mutation of p53 and p16 Tumor Suppressor Genes in Cancer and Precancerous Lesions of the Gallbladder

Yoon, Yong Bum; Kim, Chung Yong; Kim, Woo Ho; Kim, Sun Whe; Kim, Yong Tae; Ryu, Ji Kon; Lee, Woo Jin

Abstract

BACKGROUND/AIMS: The purpose of this study was to analyze the frequencies of p53 and p16 gene mutations in gallbladder cancer and precancerous lesions such as dysplasia or adenoma.
METHODS
Tissues of 13 gallbladder cancers, 3 dysplasias and 2 adenomas were collected consecutively and microdissected under a microscope. DNA was extracted from the samples. Mutations in exon 5-8 of p53 and exon 1 and 2 of p16 were detected by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP). Then, p53 DNA from bands showing mobility shifts were extracted and sequenced.
RESULTS
Mutation of p53 was detected in 5 (38%) and p16 mutations in 4 (30%) of 13 gallbladder cancers, respectively. However, neither p53 nor p16 mutation was detected in the dysplasia or the adenoma cases. All the 5 mutations of p53 were single point mutations which occurred in the highly conserved region, and resulted in amino acid substitution. Four of the 5 mutations occurred at the hot spots of p53. All of the p53 and the p16 gene mutations were observed in advanced cancers (stage II, III, IV), but were not correlated with the presence of gallstones or the histologic grade.
CONCLUSIONS
The mutations of tumor suppressor genes like p53 and p16 play a role in the pathogenesis of gallbladder cancer, but do not contribute to the development of precancerous lesions.