| Summary: | 碩士 === 國立陽明大學 === 生物醫學資訊研究所 === 96 === Hepatocellular carcinoma (HCC) is one of the most common malignant tumors and has the fifth highest mortality rate worldwide. HCC causes more than 600,000 deaths worldwide per year. In Taiwan, according to the data which is published in 2007 by the Department of Health, HCC has the second highest mortality rate out of all cancer types, accounting for 7,809 deaths that year. According to statistics, males are more likely to receive HCC than females. Male’s likelihood of death from this disease is also 2.6 times higher. Previous studies have shown that chromosomal aberrations are common in HCC. Molecular characterizations of HCC have indicated frequent loss of heterozygosity on chromosome 4q in early liver carcinogenesis.
TP53 encodes p53 protein, a DNA-binding protein that plays a major role in preventing tumor development. Previous studies have shown that p53 mutations can be found in 50% to 60 % of human cancers. These mutations are point mutation which are frequently happens in the DNA-binding domain from exon4 to exon9. The mutations abolish the activity and function of p53 on the transcription regulation for other genes.
In this study, tumor samples and normal tissues (adjacent to the tumor) were collected from 78 liver cancer patients. Of those, 47% (37/78) has loss of chromosome4q and 47% (37/78) showed mutations of the p53 gene: 32% (25/78) of patients have both. There is a significant link between the mutations of the p53 gene and the loss of chromosome4q. (p=0.0072256)
19 cases were analyzed using cDNA microarrays. Out of the cases with mutation of the p53 gene 14 genes(RAP1B、PARP4、PPAN、ZNF471、SPRY1、CTSO、FAM73B、DNAJB14、ZNF468、COBRA1、LRCH3、SETD8、MGC52000、C1orf159). were identified to be expressed differently between those that loss of chromosome4q and those that don’t. It is possible that mutation of p53 gene leads to loss of chromosome4q.
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