Loss of heterozygosity and analysis of mutation of p53 in hepatocellular carcinoma
| Autor: | Takao Tsuji, Kazuo Hamaya, Hajime Hada, Tadashi Hanafusa, Yasuhiro Yumoto, Norio Koide, Noriyuki Shinji, Souhei Ooguchi, Tsuyoshi Mitani, Takechiyo Morita |
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| Rok vydání: | 1995 |
| Předmět: |
Heterozygote
Carcinoma Hepatocellular Hepatitis C virus Hepacivirus Biology medicine.disease_cause Polymerase Chain Reaction Loss of heterozygosity medicine Carcinoma Humans Point Mutation Hepatitis Antibodies Genes Retinoblastoma neoplasms Gene Polymorphism Single-Stranded Conformational Hepatitis B virus Hepatitis B Surface Antigens Polymorphism Genetic Hepatology Retinoblastoma Liver Neoplasms Gastroenterology Chromosome Hepatitis C Antibodies medicine.disease Genes p53 digestive system diseases Blotting Southern Hepatocellular carcinoma Cancer research DNA Probes Polymorphism Restriction Fragment Length |
| Zdroj: | Journal of gastroenterology and hepatology. 10(2) |
| ISSN: | 0815-9319 |
| Popis: | Thirty-six hepatocellular carcinoma (HCC) tissues obtained from 34 patients were classified according to histological diagnosis into six well-differentiated HCC, 20 moderately differentiated HCC and 10 poorly differentiated HCC. High molecular weight DNA was prepared from each tumour and the corresponding non-tumour tissue. Loss of heterozygosity (LOH) on chromosomes 4q, 5q, 10q, 11p, 16q, 17p, mutation of the p53 gene and polymorphism of intron 25 of the retinoblastoma (RB) gene were simultaneously analysed. The patients were composed of three cases of small HCC (the diameter of which was < 3 cm) and 31 cases of advanced HCC. Twenty-nine of 34 (85.3%) patients analysed had been exposed to hepatitis B virus and/or hepatitis C virus. The frequencies of LOH on seven chromosomes were 57.9% in 17p13.3, 45.1% in 17p, 45.1% in 11p, 41.9% in 5q, 41.9% in 16q24, 29.0% in 4q, 25.8% in 10q in advanced HCC (four of well differentiated, 18 of moderately differentiated and nine of poorly differentiated carcinoma). In contrast, LOH was observed on 4q, 5q, 16q and 17p in 33% (1/3) of the small HCC (two of well differentiated and one of moderately differentiated carcinoma). The mutation of the p53 genes and polymorphism of the RB gene were present in 25.8% (8/31) and 12.9% (4/31) of the advanced tumours, respectively, but the mutation was not found in small HCC. LOH on every chromosome and the p53 mutation were observed more frequently in more advanced tumours, and the genetic changes accumulated with the increase of the histopathological grade. These findings suggest that the accumulation of genetic changes in multiple tumour suppressor genes is involved in the progression of HCC. |
| Databáze: | OpenAIRE |
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