Microsatellite Instability in Korean Hepatocellular Carcinoma using Fluorescent - PCR / 대한암학회지

PURPOSE: Hepatocellular carcinoma (HCC) is one of the most common cancers in many parts of the world, however the molecular mechanisms underlying liver cell transformation remain obscure. The instability of microsatellite sequences dispersed in the genome has been linked to a deficiency in cellular mismatch repair. This phenotype has been frequently observed in various human neoplasms and is regarded as a major factor in tumorigenesis. To investigate cumulative genetic changes related with apoptosis during development and progression of HCC, we examined DNAs isolated from 12 Korean HCCs and their adjacent non-tumorous parts to look for evidence of microsatellite instability (MSI). MATERIALS AND METHODS: Twelve microsatellite loci (D6S271, D6S426, D13S153, D13S263, D17S849, D17S938, D17S945, D18S474, D18S64, D19S420, D.19S418 and D19S210) were amplified by PCR from 12 Korean HCCs, and analyzed using an automated DNA analyzer. RESULTS: The high percentages of the MSI were found for the loci of D6S426 (33.3%) and D17S945 (25.0%). The related genes with high frequency of MSI were noted in the wafl (41.7%) and p53 (25.0%). From this study, fifty eight percent of HCCs (7/12) showed MSI with at least one marker. CONCLUSION: This results suggest that the analysis of MSI in HCC might be useful for identifying genes whose loss of function contributes to the development of liver cancer. Furthennore, this method may give a more rapid and accurate sizing of the PCR products of microsatellite; making the routine assessment of MSI possible in many clinical fields.

The apolipoprotein E genotyping using the PCR-RFLP was useful to linkage analysis of Alzheimer's disease families

Apolipoprotein E (ape E) has three common alleles (ape epsilon 2, epsilon 3 and epsilon 4) that code for three major isoforms E2, E3 and E4. The isoforms differ from each other by a single amino acid substitutions at two positions and also differ in their binding affinity for the apo E receptors. Moreover, recently a strong association between the apo epsilon 4 allele and late-onset Alzheimer disease (AD) was demonstrated. In this study, were analyzed the apo E genotypes using the Hhal digestion of PCR amplified samples, and the apo epsilon 4 allele frequency from 70 AD patients and 106 normal population in Korea. The results suggested that the frequency of epsilon 4 allele among the AD patients (35.7%) was 3 times higher than that among the control population (13.7%). The data, which are in agreement with recent reports, suggests that the apo epsilon 4 allele is associated with AD in Korea.

Deletions of 9p21 and TP53 in bladder cancer

The objective of this study was to characterize the alterations of 9p21 and TP53 in Korean transitional bladder cancer and to assess the relationship between the histopathologic parameter and the alteration of these genes. Allele loss in 29 surgically resected transitional cell carcinoma was examined by using the multiplex PCR with 7 and 1 microsatellite markers for 9p21 and TP53, respectively. Twenty-one (72%) demonstrated allele loss at 9p21 and/or TP53. Deletion at the 9p21 region was detected in 17(61%) of 28 informative cases at one or more loci, and LOH at TP53 was found in 12(55%) of 22 informative cases. Of 7 microsatellite markers for 9p21, allele loss occurred the most frequently at locus D9S162(69%) and D9S104(69%). Additionally, hemizygous deletion was slightly more common than homozygous deletion. Deletion at 9p21 and TP53 was not related with increased grade. These results suggest that the alteration of 9p21 may be an early event in the development of Korean bladder cancer, while p53 gene may be involved in early event of some bladder cancers as well as in their late events.