• Communications for Statistical Applications and Methods
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• 제13권1호
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• pp.167-175
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• 2006

It has long been recognized that cancer is a genetic disease. To find this measures of genetic instability, stain cells with chromosome specific probes using chromosome in-situ hybridization technique is adopted. Even though in-situ hybridization technique is powerful, truncation of nuclei often results in under-representation of chromosome copies in slides due to the sectioning of tissue blocks. Because of this problem we suggest three different methods to analyze the cervical cancer data set. We observe that genetic instability is an increasing function of histology and our suggested model is the best in detecting genetic instability of tumorigenesis processes.

• Molecules and Cells
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• 제37권10호
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• pp.713-718
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• 2014

Alteration in chromosome numbers and structures instigate and foster massive genetic instability. As Boveri has seen a hundred years ago (Boveri, 1914; 2008), aneuploidy is hall-mark of many cancers. However, whether aneuploidy is the cause or the result of cancer is still at debate. The molecular mechanism behind aneuploidy includes the chromosome mis-segregation in mitosis by the compromise of spindle assembly checkpoint (SAC). SAC is an elaborate network of proteins, which monitor that all chromosomes are bipolarly attached with the spindles. Therefore, the weakening of the SAC is the major reason for chromosome number instability, while complete compromise of SAC results in detrimental death, exemplified in natural abortion in embryonic stage. Here, I will review on the recent progress on the understanding of chromosome missegregation and cancer, based on the comparison of different mouse models of BubR1, the core component of SAC.

• Asian Pacific Journal of Cancer Prevention
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• 제15권3호
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• pp.1119-1123
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• 2014

Head and neck cancers (HNC) are extremely complex disease types and it is likely that chromosomal instability is involved in the genetic mechanisms of its genesis. However, there is little information regarding the background levels of chromosome instability in these patients. In this pilot study, we examined spontaneous chromosome instability in short-term lymphocyte cultures (72 hours) from 72 study subjects - 36 newly diagnosed HNC squamous cell carcinoma patients and 36 healthy ethnic controls. We estimated chromosome instability (CIN) using chromosomal aberration (CA) analysis and nuclear level anomalies using the Cytokinesis Block Micronucleus Cytome Assay (CBMN Cyt Assay). The proliferation rates in cultures of peripheral blood lymphocytes (PBL) were assessed by calculating the Cytokinesis Block Proliferation Index (CBPI). Our results showed a significantly higher mean level of spontaneous chromosome type aberrations (CSAs), chromatid type aberration (CTAs) dicentric chromosomes (DIC) and chromosome aneuploidy (CANE UP) in patients (CSAs, $0.0294{\pm}0.0038$; CTAs, $0.0925{\pm}0.0060$; DICs, $0.0213{\pm}0.0003$; and CANE UPs, $0.0308{\pm}0.0035$) compared to controls (CSAs, $0.0005{\pm}0.0003$; CTAs, $0.0058{\pm}0.0015$; DICs, $0.0005{\pm}0.0003$; and CANEUPs, $0.0052{\pm}0.0013$) where p<0.001l. Similarly, spontaneous nuclear anomalies showed significantly higher mean level of micronuclei (MNi), nucleoplasmic bridges (NPBs) and nuclear buds (NBUDs) among cases (MNi, $0.01867{\pm}0.00108$; NPBs, $0.0156{\pm}0.00234$; NBUDs, $0.00658{\pm}0.00068$) compared with controls (MNi, $0.00027{\pm}0.00009$; NPBs, $0.00002{\pm}0.00002$; NBUDs, $0.00011{\pm}0.00007$).The evaluation of CBPI supported genomic instability in the peripheral blood lymphocytes showing a significantly lower proliferation rate in HNC patients ($1.525{\pm}0.005552$) compared to healthy subjects ($1.686{\pm}0.009520$) (p<0.0001). In conclusion, our preliminary results showed that visible spontaneous genomic instability and low rate proliferation in the cultured peripheral lymphocytes of solid tumors could be biomarkers to predict malignancy in early stages.

• Molecules and Cells
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• 제37권2호
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• pp.95-99
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• 2014

Cancer is unique amongst human diseases in that its cellular manifestations arise and evolve through the acquisition of somatic alterations in the genome. In particular, instability in the number and structure of chromosomes is a near-universal feature of the genomic alterations associated with epithelial cancers, and is triggered by the inactivation of tumour suppressor mechanisms that preserve chromosome integrity in normal cells. The nature of these mechanisms, and how their inactivation promotes carcinogenesis, remains enigmatic. I will review recent work from our laboratory on the tumour suppressor BRCA2 that addresses these issues, focusing on new insights into cancer pathogenesis and therapy that are emerging from improved understanding of the molecular basis of chromosomal instability in BRCA2-deficient cancer cells.

• 대한임상검사과학회지
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• 제41권1호
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• pp.6-10
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• 2009

Ring chromosome occurs when both telomeres of a chromosome are lost and the remaining portion of the chromosome circularizes to re-establish chromosome stability. This abnormal structure shows mitotic instability unlike the normal chromosomes, causing problems during mitosis. Here, we report one case of "chromosome 4 ring syndrome" on a 6-month-old male patient with growth retardation. Ring chromosome, monosomy, dicentric chromosome were shown by conventional chromosome analysis using peripheral blood. Peripheral blood was used and incubated for 72 hours for chromosome analysis. 3 probes (LSI WHS SpectrumOrange/CEP 4 SpectrumGreen, 4p subtelomere probe, 4q subtelomere probe) were used to detect the origin and breakpoint of ring chromosome 4 by FISH (fluorescense in situ hybridization) technique.

• Clinical and Experimental Pediatrics
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• 제57권7호
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• pp.333-336
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• 2014

Reports of constitutional ring chromosome 22, r(22) are rare. Individuals with r(22) present similar features as those with the 22q13 deletion syndrome. The instability in the ring chromosome contributes to the development of variable phenotypes. Central nervous system (CNS) atypical teratoid rhabdoid tumors (ATRTs) are rare, highly malignant tumors, primarily occurring in young children below 3 years of age. The majority of ATRT cases display genetic alterations of SMARCB1 (INI1/hSNF5 ), a tumor suppressor gene located on 22q11.2. The coexistence of a CNS ATRT in a child with a r(22) is rare. We present a case of a 4-month-old boy with 46,XY,r(22)(p13q13.3), generalized hypotonia and delayed development. High-resolution microarray analysis revealed a 3.5-Mb deletion at 22q13.31q13.33. At 11 months, the patient had an ATRT ($5.6cm{\times}5.0cm{\times}7.6cm$) in the cerebellar vermis, which was detected in the brain via magnetic resonance imaging.

• Molecules and Cells
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• 제22권3호
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• pp.360-363
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• 2006

Human endogenous retroviruses (HERVs) contribute to various kinds of genomic instability via rearrangement and retrotransposition events. In the present study the formation of a new human-specific solo-LTR belonging to the HERV-H family (AP001667; chromosome 21q21) was detected by a comparative analysis of human chromosome 21 and chimpanzee chromosome 22. The solo-LTR was formed as a result of an equal homologous recombination excision event. Several evolutionary processes have occurred at this locus during primate evolution, indicating that mammalian-wide interspersed repeat (MIR) and full-length HERV-H elements integrated into hominoid genomes after the divergence of Old World monkeys and hominoids, and that the solo-LTR element was created by recombination excision of the HERV-H only in the human genome.

• Journal of Ginseng Research
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• 제46권3호
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• pp.481-488
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• 2022

Background: Although the tumor-suppressive effects of ginsenosides in cell cycle have been well established, their pharmacological properties in mitosis have not been clarified yet. The chromosomal instability resulting from dysregulated mitotic processes is usually increased in cancer. In this study, we aimed to investigate the anticancer effects of ginsenoside Rg1 on mitotic progression in cancer. Materials and methods: Cancer cells were treated with ginsenoside Rg1 and their morphology and intensity of different protein were analyzed using immunofluorescence microscopy. The level of proteins in chromosomes was compared through chromosomal fractionation and Western blot analyses. The location and intensity of proteins in the chromosome were confirmed through immunostaining of mitotic chromosome after spreading. The colony formation assays were conducted using various cancer cell lines. Results: Ginsenoside Rg1 reduced cancer cell proliferation in some cancers through inducing mitotic arrest. Mechanistically, it inhibits the phosphorylation of histone H3 Thr3 (H3T3ph) mediated by Haspin kinase and concomitant recruitment of chromosomal passenger complex (CPC) to the centromere. Depletion of Aurora B at the centromere led to abnormal centromere integrity and spindle dynamics, thereby causing mitotic defects, such as increase in the width of the metaphase plate and spindle instability, resulting in delayed mitotic progression and cancer cell proliferation. Conclusion: Ginsenoside Rg1 reduces the level of Aurora B at the centromere via perturbing Haspin kinase activity and concurrent H3T3ph. Therefore, ginsenoside Rg1 suppresses cancer cell proliferation through impeding mitotic processes, such as chromosome alignment and spindle dynamics, upon depletion of Aurora B from the centromere.

• Journal of Genetic Medicine
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• 제4권1호
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• pp.80-83
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• 2007

고리염색체(Ring chromosome)는 매우 낮은 빈도로 발견되는 염색체 이상으로 모든 번호에서 보고되고 있으며 특히 끝곁 매듭 염색체(acrocentric chromosome)에서 빈번하게 관찰 된다. 본 증례는 ring chromosome(고리염색체)11의 산전진단에 관한 것이다. 산모는 36세의 여성으로 모체혈청검사에서 에드워드 증후군의 표시인자가 증가되어, 태아의 염색체 검사를 위해 임신 19.5주에 양수천자술을 시행하였다. 결과는 46,XX,r(11)[65]/45,XX,-11[16]/46,XX[34]로 고리염색체(ring chromosome) 11이 mosaic으로 관찰되었다. 혈액을 이용한 부모 염색체 검사는 모두 정상이었다. 임신 20주에 실시된 정밀초음파 검사에서는 자궁내성장장애(IUGR) 소견을 보였다. 모자익시즘의 확인을 위해 임신 22주에 재대 혈액을 이용한 두번째 염색체 검사 결과는 46,XX,r(11)(p15.5q24.2)[229]/45,XX,-11 [15]이었으며 첫번째 검사에서 관찰되지 않았던 다양한 형태의 고리염색체(ring chromosome)가 소수의 세포에서 관찰되었다. 고리염색체(ring chromosome)11에 대한 FISH 검사에서는 11 염색체의 장완과 11 염색체의 단완의 subtelomeric 부위가 결실되어 있었다.

• BMB Reports
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• 제56권4호
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• pp.216-224
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• 2023

Centrosome abnormalities are hallmarks of human cancers. Structural and numerical centrosome abnormalities correlate with tumor aggressiveness and poor prognosis, implicating that centrosome abnormalities could be a cause of tumorigenesis. Since Boveri made his pioneering recognition of the potential causal link between centrosome abnormalities and cancer more than a century ago, there has been significant progress in the field. Here, we review recent advances in the understanding of the causes and consequences of centrosome abnormalities and their connection to cancers. Centrosome abnormalities can drive the initiation and progression of cancers in multiple ways. For example, they can generate chromosome instability through abnormal mitosis, accelerating cancer genome evolution. Remarkably, it is becoming clear that the mechanisms by which centrosome abnormalities promote several steps of tumorigenesis are far beyond what Boveri had initially envisioned. We highlight various cancer-promoting mechanisms exerted by cells with centrosome abnormalities and how these cells possessing oncogenic potential can be monitored.