| Keywords | Hepatocellular carcinoma, / Tumor suppresser gene, / p53, / LOH, / RB, / HBV, / HCV, / RLGS, / AP-PCRSSCP |
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| Research Abstract |
The mechanisms of development of HCC is still unclear the examination of genetic changes in tumor suppresser genes and oncogenes should be a valuable to elucidate the mechanisms of carcinogenesis. Frequent allelic losses at loci on chromosomes 4q, 5q, 11p, 13q, and 17p have been reported. Eighty percents of patients analyzed had been exposed to hepatitis B virus (HBV) and/or hepatitis C virus (HCV). The frequenciea of LOH on seven chromosomes were 57.9% in 17p13.3,45.1% in 17p, 45.1% in 11p, 41.9% in5q, 41.9% in 16q24,29.0% in 4q, 25.8% in advanced HCCs (4 of well differentiated, 18 of moderately differentiated and of poorly differentiated carcinoma). On the contrary LOH was observed on 4q, 5q, 16q, and 17p in 33% (1/3) of the small HCCs (2 of well differentiated, and one of moderately differentiated carcinoma). The mutation of the p53 genes and polymorphism of the RB gene were presen in 25.8% (8/31) and 12.9% (4/31) of the advanced tumor respectively, but the mutation was not found in
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small HCC.LOH on every chromosome and p53 mutation were observed more frequently in more advanced tumors, and the genetic changes accumulated with the increase of the histological grade. These findings suggest that the of genetic changes in multiple tumor suppresser genes are involved in the progression of HCC.
We examined mutations of p53 by PCR-SSCP analysis and the configuration of HBV by genetic southern hybridization in 39 HCC tissues. Although there was no statistical significance, the frequency of the mutations of p53 in HBs antigen-positive negative samples (three of 15 (20%)) was slightly lower than that HBs antigen samples (seven of 16 (44%)). The mutations were detected in HCCs that have integrated HBV DNA (three of 10) and on HBV DNA (eight of 22), but was not detected in the HCCs which had free HBV (none of seven). These observations suggested that p53 and the HBV replication are associated with the development of HCC.Polymorphism of the RB gene were present in 25.8% (8/31) and 12.9% (4/31) of the advanced tumor respectively, but the mutation was not found in small HCC.LOH on every chromosome and p53 mutation were observed more frequently in more advanced tumors, and the genetic changes accumulated with the increase of the histological grade. These findings suggest that the accumulation of genetic changes in multiple tumor suppresser genes are involved in the progression of HCC.
We examined mutations of p53 by PCR-SSCP analysis and the configuration of HBV by genetic southern hybridization in 39 HCC tissues. Although there was no statistical significance, the frequency of the mutations of p53 in HBs antig (three of 15 (20%) was slightly lower than that in HBs antigen negative samples (seven The mutations were detected in HCCs that have integrated HBV DNA (three of 10) and no HBV DNA eight of 22) but was not detected in the HCCs which had free HBV (none of seven) These observations suggested that p53 and the HBV replication are associated with the developm HCC.Alteration of genomic DNAs in HCCs were examined by restriction landmark genomic scanning (RLGS) and AP-PCR-SSCP analysis. Five spots were more intense in 10-14 in the 16HCCs (63-88%). The intensity of several spots was reduced to about half, suggesting the loss of one of two alleles.. the use of landmarks that show a reproducible increase or decrease in intensity is discussed in conjunction with future studies of genomic alteration inherent in HCC. Less
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