Deletion of chromosomes 9p and 17 associated with abnormal expression of p53, p16/MTS1 and p15/MTS2 gene protein in hepatocellular carcinomas  

作　　者：邵建永 李宇红 李晓明 吴秋良 侯景辉 刘宗石 

机构地区：[1]Cancer Center,SunYat Sen University of Medical Sciences [2]Department of Anatomical and Cellular Pathology,Faculty of Medicine,The Chinese University of HongKong,Prince of Wales Hospital

出　　处：《Chinese Medical Journal》2000年第9期49-54,共6页中华医学杂志（英文版）

基　　金：ThisworkwassupportedbytheResearchGrantCommittee ;HongKong (No CU95 6 6 1/UPG)

摘　　要：Fifteen loci on chromosome 9p and 17 were analyzed to clarify the involvement of loss of heterozygosity (LOH) in hepatocellular carcinoma (HCC) in Chinese patients positive for hepatitis B (HBV) and/or hepatitis C (HCV) infection Expression of tumor suppressor genes (TSG) of p53, p16, and p15 gene was found to correlate with a deletion of these genes Methods Immunohistochemistry and PCR-based microsatellite polymorphism analysis techniques were used Results A high frequency of LOH was detected on chromosome 9p24 at locus D9S54 (61 8%) and 9p21, concentrated at loci D9S1747 (52 4%) and D9S1752 (51 8%) On chromosome 17, high frequent LOH was concentrated on 17p at the p53 gene locus (53 8%) and locus D17S520 (52 8%) p53 protein expression was increased in HCC, which correlated with p53 gene loss Expression of p16 and p15 protein decreased in HCC when LOH occurred at locus D9S1752 (p15 gene locus) or at locus D9S1747 and D9S1748 (p16 gene is located between these 2 loci) LOH at the p53 gene and p15 gene loci was closely associated with HBV and HCV co-infection in HCC No significant relationship between LOH and HCC clinico-pathological outcomes was observed Conclusion High frequency LOH occurs on chromosomes 9p and 17 in HCC in Chinese patients Such sites may contain several putative tumor suppressor genes critically involved in the development and/or progression of HCC Deletion of p53, p16, or p15 tumor suppressor genes may cause abnormal expression of the protein product of these genes HBV and/or HCV infection may be closely associated with LOH p53 and/or p15 gene expressionFifteen loci on chromosome 9p and 17 were analyzed to clarify the involvement of loss of heterozygosity (LOH) in hepatocellular carcinoma (HCC) in Chinese patients positive for hepatitis B (HBV) and/or hepatitis C (HCV) infection Expression of tumor suppressor genes (TSG) of p53, p16, and p15 gene was found to correlate with a deletion of these genes Methods Immunohistochemistry and PCR-based microsatellite polymorphism analysis techniques were used Results A high frequency of LOH was detected on chromosome 9p24 at locus D9S54 (61 8%) and 9p21, concentrated at loci D9S1747 (52 4%) and D9S1752 (51 8%) On chromosome 17, high frequent LOH was concentrated on 17p at the p53 gene locus (53 8%) and locus D17S520 (52 8%) p53 protein expression was increased in HCC, which correlated with p53 gene loss Expression of p16 and p15 protein decreased in HCC when LOH occurred at locus D9S1752 (p15 gene locus) or at locus D9S1747 and D9S1748 (p16 gene is located between these 2 loci) LOH at the p53 gene and p15 gene loci was closely associated with HBV and HCV co-infection in HCC No significant relationship between LOH and HCC clinico-pathological outcomes was observed Conclusion High frequency LOH occurs on chromosomes 9p and 17 in HCC in Chinese patients Such sites may contain several putative tumor suppressor genes critically involved in the development and/or progression of HCC Deletion of p53, p16, or p15 tumor suppressor genes may cause abnormal expression of the protein product of these genes HBV and/or HCV infection may be closely associated with LOH p53 and/or p15 gene expression

关 键 词：hepatocellular carcinoma loss of heterozygosity CHROMOSOME tumor suppressor gene hepatitis virus 

分 类 号：R735.7[医药卫生—肿瘤]