K-ras Mutations in Hepatocellular Carcinomas
C Liu, D Cardona, HJ Dong. University of Florida, Gainesville, FL
Background: K-ras mutations are detected in many types of human cancers. Mutation status of this gene plays a critical role in guiding clinical therapy for colon cancer. K-ras mutations have been detected in hepatocellular carcinomas (HCC) induced in animal models, but the characteristics of K-ras mutations and their clinical significance in human HCCs have not been well studied. The objective of our study is to examine and characterize K-ras mutations in HCC.
Design: Fifty-two cases of HCC and forty cases of colorectal carcinomas (CRC) were selected for K-ras mutation analysis. Total DNA was extracted from formalin-fixed tissue using Waxfree DNA extraction kit according to the manufacturer's instructions. K-ras gene region was amplified by PCR using a pair of gene-specific primers with the forward primer labeled with biotin. Three sequence-specific primers that are designed for detecting mutations at codon 12 or 13 were then used for pyrosequencing analysis. The mutant group and the wild type group were compared regarding clinical parameters and histological features. Student's t test was used for statistical analysis.
Results: K-ras mutations were detected in 11 out of total 52 cases (21%) of HCCs, while K-ras mutations were detected in 15 out of total 40 cases (38%) of CRCs. In contrast to CRCs that have both codon 12 and 13 mutations, the K-ras mutations in HCC are exclusively in codon 12. Among the 11 cases of HCCs with K-ras codon 12 mutations, 8 cases have hepatitis C viral (HCV) infection (72%); Among the K-ras wild type cases, 18 out of 45 have HCV infection (40%). The difference is statistically significant (p value is 0.006). Compared with the K-ras mutant and K-ras wild type groups, the average age in the K-ras mutant group is 54.8 year-old and the average age in the K-ras wild type group is 58.2 year-old. There is no significant difference in tumor differentiation, vascular invasion, or tumor stage between the two groups.
Conclusions: From this study, we conclude that: 1. K-ras mutations can be detected in 21% of human HCCs; 2. K-ras mutation in HCC occurs exclusively at codon 12; 3. K-ras mutation appears to be associated with higher incidence in HCCs with underlying HCV chronic infection.
Category: Liver & Pancreas
Tuesday, March 23, 2010 9:30 AM
Poster Session III # 229, Tuesday Morning