Loss of heterozygosity of the tumor suppressor gene Tg737 in the side population cells of hepatocellular carcinomas is associated with poor prognosis.

Analysis of loss of heterozygosity (LOH) is a useful method for finding genetic alterations in tumor and precancerous lesion tissues. In this study, we analyzed LOH of the tumor suppressor gene Tg737 in side population cells of human hepatocellular carcinomas. Side population cells were sorted and identification by flow cytometry from suspensions of hepatocarcinoma or normal liver cells generated from 95 hepatocellular carcinoma and normal tissues, respectively. DNA was extracted from the two groups of side population cells and peripheral blood specimens. Five microsatellite markers on the Tg737 gene were used to analyze the frequency of loss of heterozygosity in the side population cells of the hepatocellular carcinoma. Twenty-four (25.30%) tumor samples had a large deletion in more than three microsatellite markers. The highest frequency of loss of heterozygosity was observed with the G64212 marker (78.75%) and the SHGC-57879 marker (75.95%). Statistical analysis of the correlation between loss of heterozygosity of Tg737 and clinicopathological features indicated a strong correlation between the two markers associated with the highest frequency of loss of heterozygosity and survival. The results indicate that loss of heterozygosity of the tumor suppressor gene Tg737 may play an important role in the carcinogenetic mechanism of liver cancer stem cells. In addition, the independent association between loss of heterozygosity at the SHGC-57879 and G64212 markers and worsened short-term survival in patients could be used as a novel prognostic predictor. Further studies of side population cells may contribute to the establishment of novel therapeutic strategies for hepatocellular carcinoma.