Amplification of Extrachromosomal Oncogene and Tumorigenesis and Development / 中国肺癌杂志

Extrachromosomal DNA (ecDNA) is a small segment of circular DNA located outside the chromosome, which has the function of self-replication. Recently, amplification of oncogenes on ecDNA has been proved to be a common phenomenon in tumor cells, and has some characteristics worth studying, such as correlation with patients' poor prognosis. Multiple chromosomal events are involved in the formation of ecDNA, and its amplification can directly increase the number of DNA copies of extra-chromosomal oncogenes and accelerate the generation and development of tumors. Moreover, the segregation pattern of unequal transmission of parental ecDNA cells to offspring not only increases tumor heterogeneity, but also enhances tumor adaptation to environment and response to therapy. This article reviews the current status and potential significance of ecDNA in tumor cells.
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Double Minutes Containing C-MYC oncogene with a Normal Karyotype in Acute Myelogenous Leukemia: A Case Report / 대한진단검사의학회지

We report a case of a female karyotype that was normal except for double minutes (dmin) in acute myeloid leukemia. Using fluorescence in situ hybridization, the amplification of C-MYC was detected in both interphase and metaphase cells. The patient of the present case had received only limited therapy with cytosine arabinoside, but lived for more than one year. It supports the recent notion that dmin may not necessarily be associated with a poor outcome.

Establishment of Korean Neuroblastoma Cell Line (NBL-K1) / 대한소아혈액종양학회지

PURPOSE: A new continuous cell line, NBL-K1, was established in tissue culture from a Korean child with stage IV neuroblastoma, arising from the adrenal gland, which had normal urinary excretion of VMA and HVA and diagnosed by light and electron microscope. METHODS: Clinical characteristics of patient was high ferritin level, normal neuron specific enolase, and normal urinary VMA and HVA. The small tissue specimen obtained from surgically resected tumor was minced with a mosquito scissors and scalpels and cultured in L-15 medium with 17% FBS (37oC and 5% CO2). Chromosome analysis was performed from bone marrow cell culture with a method of high resolution banding using methotrexate and thymidine and TGT staining. Chromosomes were analyzed by ISCN. The N-myc amplification was checked by N-myc primers, PCR, and gel electrophoresis. RESULTS: The cells were attached to the bottom of culture flask on 4th day of culture and composed of a small and elongated cell body with relatively abundant granules in cytoplasm and oval shaped nucleus with one prominent nucleoli and slender nerve-like fiber. Cell clumps were observed on 10th day of culture. The morphology was changed to round cell when trypsin was added. The chromosome analysis revealed two kinds of hyperdiploidy. No cell contained homogeneously stained region (HSR). But numerous double minutes (DMs) were observed. N- myc oncogene of the NBL-K1 was not amplified. The cultured cells with many black immunobeads around the surface considered to be the neuroblastoma cells. CONCLUSION: The characteristic Korean neuroblastoma cell line (NBL K-1) was estblished for the future studies of in vitro chemosensitivity test, monoclonal antibody and xenograft.

In Vitro Chemosensitivity Test for Neuroblastoma Cells / 대한소아혈액종양학회지

PURPOSE: Neuroblastoma is the second common solid tumor in chidhood and has the worst prognosis in stage IV case. To improve the future survival rate in this disease the clinical and laboratory characteristics of patients, the characteristics and chemosensitivity test of cultured neuroblastoma cells and the outcome were compared. METHODS: The clinical characteristics including age, urinary catecholamines, serum ferritin, neuron specific enolase, pathology, stage, and patient's outcome were evaluated in four neuroblastoma patients diagnosed at the Department of Pediatrics, Kyungpook National Univesity Hospital. The neuroblastoma cells obtained from tumor or bone marrow cells were cultured and used for immunobead test using mononuclear antibody, biochemical analysis, N-myc oncogene copy, chromosome study and chemosensitivity test. Cyclophosphamide, cisplatin, doxorubicin, etoposide, ifosfamide and melphalan were used in chemosensitivity test. The statistical analyses were done by chi2-method. RESULTS: The age of patients were 6~31 (mean; 18) months. The adrenal gland was the primary site and the stage was IV in all cases. In laboratory data, serum ferritin level were 40~352 (204) ng/mL, neuron specific enolase 45~167 (107) ng/mL, urinary excretion of HVA 1.8~268 (73) mg/day, of VMA 0.2~345 (87) mg/day and the HVA/VMA ratio 0.8~67 (20). Cultured neuroblastoma cells and immunobeads attached around the cell were observed. The partial deletion of short arm or monosomy of chromosome 1, double minutes or homogenous stained region were found in three patients. N-myc oncogene copy was positive in one of two tested. Radical surgery was done in three patients and chemotherpy and radiotherpy by CCG-3881 or -3891 were given in four patients. The duration of survival in three died patients were 6~13 (mean; 10) months. One is survived in relapse-free state for 52 months. In chemosensitivity test, the neuroblastoma cell of survivor was highly sensitive in all drugs compared to the neuroblastoma cell of relapsed patients. CONCLUSION: Normal serum ferritin level or normal chromosome were correlated as a good prognostic factors in survivor compare in relapsed patients. In chemosensitivity test, the neuroblastoma cells of survivor were higher sensitive to all drugs compare to those of relapsed patients. The chemosensitivity test of this method were relatively simple and could be used in selection of anticancer drug and as a prognostic factor in neuroblastoma.

DOUBLE MINUTES EXPRESSION AND ITS SIGNIFICANCE IN PREOPERATIVE AND POSTOPERATIVE PATIENTS WITH BLADDER TRANSITIOAL CELL CARCINOMA / 解剖学报

Objective To investigate the expression of double minutes (DM) in bladder transitional cell carcinoma (TCC) and its significance. Methods 15 control individuals and 14 patients were examined. Whole blood samples from these patients were cultured before and 10-15 days after operations. The relationship between expression of DM and clinic-pathologic factors and prognosis was ana- lyzed by chi-square test. Results There is no DM in control individuals, but there are respectively 35 pairs and 31 pairs DM in preop- erative and optoperative patients with TCC (P 0. 05). Conclusions DM may be an independent prognosis indication of cancer gene amplication. DM always show treatment failure and rapid recurrence.