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Alteration of cell-cycle related genes in hepatocarcinogenesis
N. Nishida1, Y. Fukuda1, K. Ishizaki2 and K. Nakao1
1Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto and 2Laboratory of Experimental Radiology, Aichi Cancer Center Research Institute, Chigusaku, Nagoya, Japan
Offprint requests to: Dr. Naoshi Nishida. Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, 54
Kawahara-cho, Shogoin, Sakyoku, Kyoto 606, Japan
Summary. The mammalian cell cycle is controlled by
regulators of the G1 to S transition such as tumor
suppressor proteins, p53 and retinoblastoma (RB); cyclin
D1 and cyclin-dependent kinase 4; and inhibitor of
cyclin dependent kinase, Recently,
aberrations of these cell cycle-related genes have been
reported to contribute to the formation and development
of cancer. In human hepatocellular carcinoma (HCC),
high frequencies of aberration have been detected in the
p53 and RB genes. Loss of heterozygosity (LOH) of
chromosome 13q was detected in 35% of HCC and LOH
on chromosome 17p was detected in 49%. Mutation of
the p53 gene was also detected in 32%. The aberrations
of these genes were observed more frequently in poorly
differentiated and in advanced HCCs. On the other hand,
genetic alterations of the cyclin DI and p161NK4A genes
were not so frequent, but appeared to be associated with
the aggressive behavior of the tumor, which suggests that
disruption of the cell cycle-related genes results in the
progression of HCC. Further study with a substantial
number of cases is required to determine the actual
frequency of the aberrations of the G1 controlling genes
in hepatocarcinogenesis. Histol Histopathol 12, 1019-1025
(1997)
Key words: p53, RB, Cyclin DI, p16, Hepatocellular
carcinoma
DOI: 10.14670/HH-12.1019
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