- Loss of Heterozygosity on Chromosome 9p21, 17p13 and 3p in Human Astrocytic Tumor.
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Youn Soo Lee, Chang Suk Kang, Seung Myung Dong, Jung Yong Lee, Sang In Shim, Byung Kee Kim
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Korean J Pathol. 2001;35(4):330-337.
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 Abstract
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- BACKGROUND
The purpose of this study was to determine the genetic abnormalities of chromosomes 9p21, 17p13.1, 3p25 and 3p14.2 in the development and progression of astrocytic tumors.
METHODS
We performed loss of heterozygosity (LOH) analysis in 41 astrocytic tumors, including 20 astrocytomas, 11 anaplastic astrocytomas and 10 glioblastomas, and correlated the results of LOH at different histopathologic grades. LOH was determined by multiplex polymerase chain reaction analysis of the DNA, which was extracted by microdissection.
RESULTS
LOH of 9p21 was found in 55.6% of astrocytomas, 54.6% of anaplastic astrocytomas and 100.0% of glioblastomas. LOH of 17p13.1 was found in 21.4% of astrocytomas, 28.6% of anaplastic astrocytomas, and 66.7% of glioblastomas. LOH of 3p25 was found in 37.5% of astrocytomas, 16.7% of anaplastic astrocytomas, and 14.3% of glioblastomas. LOH of 3p14.2 was found in 16.7% of astrocytomas, 40.0% of anaplastic astrocytomas, and 42.9% of glioblastomas. LOH on chromosome 9p21 and 17p13.1 was closely related with the histopathologic grades.
CONCLUSIONS
These results may suggest that LOH of 9p21, 17p13.1, 3p25 and 3p14.2 involves an early event of astrocytoma development and accumulates during progression.
LOH of 3p25 may be involved in the tumorigenesis of astrocytoma. Identification of these LOH may illuminate the stepwise pathogenesis of astrocytic tumors and predict the possibility of malignant transformation.
- Loss of Heterozygosity at VHL, FHIT, and p16 Loci in Nonpapillary Renal Cell Carcinoma.
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Won Sang Park, Seung Myung Dong, Yong Hyun Cho, Tae Gon Hwang, Su Young Kim, Min Sun Shin, Jae Ho Pi, Suk Hyung Lee, Nam Jin Yoo, Jung Young Lee
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Korean J Pathol. 1999;33(1):8-14.
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- The objectives of this study were to characterize the alterations of 3p and 9p in sporadic renal cell carcinomas (RCC) and to assess the relationship between the clinical stages or tumor size and the alteration of these chromosomes. Thirty eight archival, paraffin embedded tissue sections from 38 patients with RCC were analyzed for loss of heterozygosity (LOH) at 3p and 9p with 11 microsatellite markers. LOH was detected in 81.6% (31/38) and 37.8% (14/37) at 3p and 9p, respectively. The frequencies of LOH at VHL and FHIT locus were 75.6% and 72.2%, respectively. Twelve cases out of 38 showed LOH at both 9p21 and 3p. The loss of 3p in the samples tested was not related to clinical stages and tumor size, but that of 9p21 was significantly associated with advanced stage and larger tumor size. These results support that 3p deletion, including VHL and FHIT gene, play a critical role in the tumorigenesis of sporadic RCC, especially at early stage, and that 9p21 may contribute to the progression of sporadic RCC.
- Identification of Zinc Finger Genes that are Differentially Expressed upon Apoptosis of Ramos B Cells.
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Min Sun Shin, Su Young Kim, Seung Myung Dong, Eun Young Na, Sug Hyung Lee, Won Sang Park, Jung Young Lee, Nam Jin Yoo
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Korean J Pathol. 1998;32(12):1043-1048.
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Abstract
- Typical programmed cell death requires de novo macromolecular synthesis and shares common morphological changes referred to as apoptosis. To elucidate the molecular mechanism of apoptosis, we isolated 13 cDNA clones of zinc finger genes that are differentially expressed in calcium ionophore-induced apoptosis of Ramos human B cell by 'targeted RNA fingerprinting' protocol (Stone & Wharton, 1993). According to DNA sequence analysis of the 13 cDNA clones, three clones are identical with ZNF7, ZNF143 and MTB-Zf, respectively, and 8 out of the other 10 clones showed partial homology to known zinc finger genes.
Differential expression was confirmed in the three known zinc finger genes by ribonuclease protection assay. ZNF7 and ZNF143 are up-regulated after induction of apoptosis, and, in contrast, MTB-Zf is down-regulated. According to the previous reports on these three genes, all of the three genes have been suspected to be tumor suppressor genes, but their functions have not been identified yet. Taken together, our results suggest that many of the novel and known zinc finger genes might play important roles in regulation of apoptosis and that these findings also provide clues as to the functions of the three putative tumor suppressor genes, ZNF7, ZNF143 and MTB-Zf in terms of apoptosis. In addition, the isolation of zinc finger genes by targeted RNA fingerprinting could be a straightforward approach for the identification of novel candidate genes associated with apoptosis.
- Identification of Differentially Expressed Genes Using RNA Fingerprinting in Cell after DNA Damage.
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Jung Young Lee, Min Sun Shin, Seung Myung Dong, Eun Young Na, Su Young Kim, Sug Hyung Lee, Won Sang Park, Nam Jin Yoo
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Korean J Pathol. 1998;32(5):321-327.
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Abstract
- RNA fingerprinting using on arbitrary primed polymerase chain reaction (RAP-PCR) was carried out to identify differentially expressed genes in HL-60 cell after treatment of methylmethane sulfonate (MMS). Twenty differentially expressed PCR products were cloned and analyzed. We have successfully obtained eight partial cDNA sequences by TA cloning method. Among these, six cDNAs were up-regulated and two cDNAs were down-regulated after the MMS treatment. Of these six up-regulated cDNAs, 3 cDNAs were equivalent to known genes in the GenBank/EMBL databases with 98~100% homology searched by BLAST program: genomic DNA fragment containing CpGg island (clone 26h8), Human Rev interacting protein-1 (RIP-1), and human zinc finger protein-4 (HZF4).
The sequences of the three remaining cDNA were entirely new genes, but we didn't try to identify a full cDNA sequence.
Two clones called KIAA0060 and KIAA0065, were down-regulated in HL-60 cells after the MMS treatment. These findings suggest that the RNA fingerprinting method using RAP-PCR is an effective method which can identify and separate the differentially expressed cDNAs and that the isolated cDNAs might involve in regulation mechanism of apoptosis and/or cell cycle delay, especially a p53-independent pathway, in the cells after DNA damage. But the nature of cDNAs that we have isolated remains to be elucidated.
- The Role of gadd and p53 Genes in Apoptosis and Cell Cycle Delay by Genotoxic Agents.
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Jung Young Lee, Jung Duk Lee, Seung Myung Dong, Eun Young Na, Min Sun Shin, Su Young Kim, Sug Hyung Lee, Won Sang Park, Nam Jin Yoo
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Korean J Pathol. 1998;32(4):239-247.
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- The aim of this study was to investigate the relationships between the gadd genes expression and an apoptosis induction in two different growing cell types after treatments with cisplatin and methylmethan sulfonate (MMS). We have examined the kinetics and specificity of gadd45 and gadd153 expression following cisplatin and MMS treatments to HL-60 cells and primary cultured human kidney (HKN) cells. We have also determined an induction time of apoptosis by DNA fragmentation analysis and the presence of the cell cycle arrest by a flow cytometric measurement. The results were as follows. In non-adherent HL-60 cells, a typical ladder pattern was observed within 4 hours after treatments of 20 micrometer of cisplatin and 100 microgram/ml of MMS. At the same time while adherent HKN cells failed to exhibit a ladder pattern at even higher doses of genotoxic agents.
Since HL-60 cells do not have p53 gene, these findings suggest the presence of a p53-independent apoptotic pathway.
The increasing patterns of the mRNA levels of gadd45 and gadd153 varied with the type of genotoxic agents. In the case of MMS treatment, the induction was rapid and transient, regardless of the cell types. The mRNA level peaked at 4 hours after MMS treatment and markedly decreased after 12 hours. On the other hand, cisplatin-induced transcriptions of gadd45 and gadd153 continued to increase for at least 24 hours and reached a peak level at 48 hours after cisplatin treatment, regardless of the cell types.
HL-60 cells revealed G2 arrest following 24 hours after cisplatin and MMS treatments. These findings suggest that the regulation mechanism of apoptosis between adherent and non-adherent cells, might be different and that gadd45 and gadd153 might have an important role in DNA repair rather than apoptosis. Also, the findings suggest that an expression pattern of gadd45 and gadd153 might be different according to the type of genotoxic agents.
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