• Title/Summary/Keyword: CIMP

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Epigenetic insights into colorectal cancer: comprehensive genome-wide DNA methylation profiling of 294 patients in Korea

  • Soobok Joe;Jinyong Kim;Jin-Young Lee;Jongbum Jeon;Iksu Byeon;Sae-Won Han;Seung-Bum Ryoo;Kyu Joo Park;Sang-Hyun Song;Sheehyun Cho;Hyeran Shim;Hoang Bao Khanh Chu;Jisun Kang;Hong Seok Lee;DongWoo Kim;Young-Joon Kim;Tae-You Kim;Seon-Young Kim
    • BMB Reports
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    • v.56 no.10
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    • pp.563-568
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    • 2023
  • DNA methylation regulates gene expression and contributes to tumorigenesis in the early stages of cancer. In colorectal cancer (CRC), CpG island methylator phenotype (CIMP) is recognized as a distinct subset that is associated with specific molecular and clinical features. In this study, we investigated the genome-wide DNA methylation patterns among patients with CRC. The methylation data of 1 unmatched normal, 142 adjacent normal, and 294 tumor samples were analyzed. We identified 40,003 differentially methylated positions with 6,933 (79.8%) hypermethylated and 16,145 (51.6%) hypomethylated probes in the genic region. Hypermethylated probes were predominantly found in promoter-like regions, CpG islands, and N shore sites; hypomethylated probes were enriched in open-sea regions. CRC tumors were categorized into three CIMP subgroups, with 90 (30.6%) in the CIMP-high (CIMP-H), 115 (39.1%) in the CIMP-low (CIMP-L), and 89 (30.3%) in the non-CIMP group. The CIMP-H group was associated with microsatellite instability-high tumors, hypermethylation of MLH1, older age, and right-sided tumors. Our results showed that genome-wide methylation analyses classified patients with CRC into three subgroups according to CIMP levels, with clinical and molecular features consistent with previous data.

DNA Methylation of Multiple Genes in Gastric Cancer: Association with CpG Island Methylator Phenotype and Helicobocter pylori Infection (위암에서 유전자 메틸화와 CpG Island Methylator Phenotype 및 Helicobacter pylori균 감염과의 연관성)

  • Jun, Kyong-Hwa;Won, Yong-Sung;Shin, Eun-Young;Cho, Hyun-Min;Im, Myoung-Goo;Chin, Hyung-Min;Park, Woo-Bae
    • Journal of Gastric Cancer
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    • v.6 no.4
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    • pp.227-236
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    • 2006
  • Purpose: Methylation of gene regulatory elements plays an important role in gene inactivation without genetic alteration. Gastric cancer is one of the tumors that exhibit a high frequency of CpG island hypermethylation. The purpose of this study was to investigate the occurrence of CpG island hypermethylation in gastric carcinoma in relation to H. pylori infection, CIMP and clincopathologic variables. Materials and Methods: We investigated the promoter methylation Status of six genes (hMLH1, p16, p14, COX-2, MGMT, E-cadherin) and CIMP in 36 gastric carcinoma tissues as well as in nontumor tissues. CIMP status was investigated by examining the methylation status of MINT 1, 2, 12, 25 and 31. The methylation status of the promoter was examined by methylation-specific PCR (MSP) and H. pylori infection was examined by histological diagnosis after staining with Warthin-Starry silver. Results: Among the 36 gastric carcinoma tissues, DNA hypermethylation was detected in the following frequencies: 14 (38.9%) for p14, 13 (36.1%) for p16, 8 (22.2%) for MGMT, 10 (27.8%) for COX-2, 21 (58.3%) for E-cadherin, and 6 (16.7%) for hMLH1. The frequencies for MINT1 and MINT25 hypermethylation were significantly higher in tumor tissues than in nontumor tissues. 16 (44.4%) of the 36 gastric carcinoma tissues were positive for the CIMP CIMP-H tumors were associated with older patients and larger tumor size than CIMP-L tumors. We found a significant association between the presence of the CIMP and hypermethylation of p16. Hypermethylation of p16 and MINT2 were significantly different when compared by age. MINT1 gene methylation was significantly associated with H. pylori infection (P=0.004). Conclusion: Our results suggest that aberrant hypermethylation of multiple tumor related genes (hMLH1, p16, p14, COX-2, MGMT, E-cadherin, MINT1, 2, 12, 25, 31) occurs frequently in gastric carcinoma tissues. The hypermethylation of MINT1 was significantly higher in the tumor tissues and was associated with H. pylori infection.

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Implementation of Cloud-Based Virtual Laboratory using SOI and CIMP on Virtual Machines

  • Ferdiansyah, Doddy;Hwang, Mintae
    • Journal of information and communication convergence engineering
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    • v.20 no.1
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    • pp.16-21
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    • 2022
  • In this research, we create a network infrastructure based on a service-oriented infrastructure (SOI) for the virtualization technology and integrate it with a cloud technology that applies the cloud integration management platform (CIMP) concept. In CIMP, the server and storage will be separated. The server will be adopted for virtualization while the storage will be used by students and teachers to store data. As long they save their data in the storage module, every time, everywhere, and on every device, they can access their data. This research will implement the design of the network infrastructure and be applied to the remote practical learning system in the laboratory. Students and teachers will ultimately adopt this network infrastructure for remote practice using their respective devices without physically meeting in the laboratory. In the future, if the implementation phase is successful, then in addition to laboratory environments, it can be implemented in all learning activities at our campus.

Analyzing the Research Fronts of Women's Studies in Korea Using Citation Image Makers Profiling (인용 이미지 구축자 프로파일링을 이용한 국내 여성학 분야 연구 전선 분석)

  • Kim, Jo-Ah;Lee, Jae Yun
    • Journal of the Korean Society for information Management
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    • v.33 no.2
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    • pp.201-225
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    • 2016
  • A new technique for revealing the research fronts of a interdisciplinary discipline has been developed. Citation image makers profiling (CIMP) determines the relationships between research papers with the title words of the citing documents. We adapted this new technique to analyze the research fronts and hot topics in women's studies of Korea. By Korean Citation Index (KCI) data in 2015, we selected 148 papers cited more than 9 times as the core documents of women's studies. Analysis of intellectual structure using citation image makers profiling was performed with the 148 core documents and those citing papers. Document co-citation analysis was hindered by citation data sparsity, while CIMP method successfully revealed the structure of research fronts of Korean women's studies including 2 divisions and 6 subdivisions. The CIMP method suggested in this study has good potential to discover the characteristics of research fronts of interdisciplinary research domains.

Deciphering the DNA methylation landscape of colorectal cancer in a Korean cohort

  • Seok-Byung Lim;Soobok Joe;Hyo-Ju Kim;Jong Lyul Lee;In Ja Park;Yong Sik Yoon;Chan Wook Kim;Jong-Hwan Kim;Sangok Kim;Jin-Young Lee;Hyeran Shim;Hoang Bao Khanh Chu;Sheehyun Cho;Jisun Kang;Si-Cho Kim;Hong Seok Lee;Young-Joon Kim;Seon-Young Kim;Chang Sik Yu
    • BMB Reports
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    • v.56 no.10
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    • pp.569-574
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    • 2023
  • Aberrant DNA methylation plays a pivotal role in the onset and progression of colorectal cancer (CRC), a disease with high incidence and mortality rates in Korea. Several CRC-associated diagnostic and prognostic methylation markers have been identified; however, due to a lack of comprehensive clinical and methylome data, these markers have not been validated in the Korean population. Therefore, in this study, we aimed to obtain the CRC methylation profile using 172 tumors and 128 adjacent normal colon tissues of Korean patients with CRC. Based on the comparative methylome analysis, we found that hypermethylated positions in the tumor were predominantly concentrated in CpG islands and promoter regions, whereas hypomethylated positions were largely found in the open-sea region, notably distant from the CpG islands. In addition, we stratified patients by applying the CpG island methylator phenotype (CIMP) to the tumor methylome data. This stratification validated previous clinicopathological implications, as tumors with high CIMP signatures were significantly correlated with the proximal colon, higher prevalence of microsatellite instability status, and MLH1 promoter methylation. In conclusion, our extensive methylome analysis and the accompanying dataset offers valuable insights into the utilization of CRC-associated methylation markers in Korean patients, potentially improving CRC diagnosis and prognosis. Furthermore, this study serves as a solid foundation for further investigations into personalized and ethnicity-specific CRC treatments.

Exploring the DNA methylome of Korean patients with colorectal cancer consolidates the clinical implications of cancer-associated methylation markers

  • Sejoon Lee;Kil-yong Lee;Ji-Hwan Park;Duck-Woo Kim;Heung-Kwon Oh;Seong-Taek Oh;Jongbum Jeon;Dongyoon Lee;Soobok Joe;Hoang Bao Khanh Chu;Jisun Kang;Jin-Young Lee;Sheehyun Cho;Hyeran Shim;Si-Cho Kim;Hong Seok Lee;Young-Joon Kim;Jin Ok Yang;Jaeim Lee;Sung-Bum Kang
    • BMB Reports
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    • v.57 no.3
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    • pp.161-166
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    • 2024
  • Aberrant DNA methylation plays a critical role in the development and progression of colorectal cancer (CRC), which has high incidence and mortality rates in Korea. Various CRC-associated methylation markers for cancer diagnosis and prognosis have been developed; however, they have not been validated for Korean patients owing to the lack of comprehensive clinical and methylome data. Here, we obtained reliable methylation profiles for 228 tumor, 103 adjacent normal, and two unmatched normal colon tissues from Korean patients with CRC using an Illumina Infinium EPIC array; the data were corrected for biological and experiment biases. A comparative methylome analysis confirmed the previous findings that hypermethylated positions in the tumor were highly enriched in CpG island and promoter, 5' untranslated, and first exon regions. However, hypomethylated positions were enriched in the open-sea regions considerably distant from CpG islands. After applying a CpG island methylator phenotype (CIMP) to the methylome data of tumor samples to stratify the CRC patients, we consolidated the previously established clinicopathological findings that the tumors with high CIMP signatures were significantly enriched in the right colon. The results showed a higher prevalence of microsatellite instability status and MLH1 methylation in tumors with high CMP signatures than in those with low or non-CIMP signatures. Therefore, our methylome analysis and dataset provide insights into applying CRC-associated methylation markers for Korean patients regarding cancer diagnosis and prognosis.

Design Analysis in a Cavity with Leadframe during Semiconductor Chip Encapsulation (반도체 칩 캡슐화(encapsulation)를 위한 트랜스퍼 금형 캐비티(cavity)에서의 설계 해석 및 실험에 관한 연구)

  • Han, Sejin;Huh, Yong-Jeong
    • Journal of the Korean Society for Precision Engineering
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    • v.12 no.12
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    • pp.91-99
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    • 1995
  • An effort has been made to more accurately analyze the flow in the chip cavity, particularly to model the flow through the openings in the leadframe and correctly treat the thermal boundary condition at the leadframe. The theoretical analysis of the flow has been done by using the Hele- Shaw approximation in each cavity separated by a leadframe. The cross-flow through the openings in the leadframe has been incorporated into the Hele-Shaw formulation as a mass source term. The temperature of the leadframe has been calculated based on energy balance in the leadframe. The flow behavior in the leadframe has been verified experimentally. In the experiment, a transparent mold and clear fluid have been used for flow visualization. Comparisons were made between the calculation and experimental results which showed a good agreement.

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Comprehensive profiling of DNA methylation in Korean patients with colorectal cancer

  • Hyeran Shim;Kiwon Jang;Yeong Hak Bang;Hoang Bao Khanh Chu;Jisun Kang;Jin-Young Lee;Sheehyun Cho;Hong Seok Lee;Jongbum Jeon;Taeyeon Hwang;Soobok Joe;Jinyeong Lim;Ji-Hye Choi;Eun Hye Joo;Kyunghee Park;Ji Hwan Moon;Kyung Yeon Han;Yourae Hong;Woo Yong Lee;Hee Cheol Kim;Seong Hyeon Yun;Yong Beom Cho;Yoon Ah Park;Jung Wook Huh;Jung Kyong Shin;Dae Hee Pyo;Hyekyung Hong;Hae-Ock Lee;Woong-Yang Park;Jin Ok Yang;Young-Joon Kim
    • BMB Reports
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    • v.57 no.2
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    • pp.110-115
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    • 2024
  • Alterations in DNA methylation play an important pathophysiological role in the development and progression of colorectal cancer. We comprehensively profiled DNA methylation alterations in 165 Korean patients with colorectal cancer (CRC), and conducted an in-depth investigation of cancer-specific methylation patterns. Our analysis of the tumor samples revealed a significant presence of hypomethylated probes, primarily within the gene body regions; few hypermethylated sites were observed, which were mostly enriched in promoter-like and CpG island regions. The CpG Island Methylator Phenotype-High (CIMP-H) exhibited notable enrichment of microsatellite instability-high (MSI-H). Additionally, our findings indicated a significant correlation between methylation of the MLH1 gene and MSI-H status. Furthermore, we found that the CIMP-H had a higher tendency to affect the right-side of the colon tissues and was slightly more prevalent among older patients. Through our methylome profile analysis, we successfully verified the methylation patterns and clinical characteristics of Korean patients with CRC. This valuable dataset lays a strong foundation for exploring novel molecular insights and potential therapeutic targets for the treatment of CRC.

Sensitive and Noninvasive Detection of Aberrant SFRP2 and MGMT-B Methylation in Iranian Patients with Colon Polyps

  • Naini, M Alizade;Mokarram, P;Kavousipour, S;Zare, N;Atapour, A;Zarin, M Hassan;Mehrabani, G;Borji, M
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.4
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    • pp.2185-2193
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    • 2016
  • Background: The pathogenesis of sporadic colorectal cancer (CRC) is influenced by the patient genetic background and environmental factors. Based on prior understanding, these are classified in two major pathways of genetic instability. Microsatellite instability (MSI) and CPG island methylator phenotype (CIMP) are categorized as features of the hypermethylated prototype, and chromosomal instability (CIN) is known to be indicative of the non-hypermethylated category. Secreted frizzled related protein 2 (SFRP2), APC1A in WNT signaling pathway and the DNA repair gene, O6-methylguanine-DNA methyltransferase (MGMT), are frequently hypermethylated in colorectal cancer. Detection of methylated DNA as a biomarker by easy and inexpensive methods might improve the quality of life of patients with CRC via early detection of cancer or a precancerous condition. Aim: To evaluate the rate of SFRP2 and MGMT hypermethylation in both polyp tissue and serum of patients in south Iran as compared with matched control normal population corresponding samples. Materials and Methods: Methylation-specific PCR was used to detect hypermethylation in DNA extracted from 48 polypoid tissue samples and 25 healthy individuals. Results: Of total polyp samples, 89.5% had at least one promoter gene hypermethylation. The most frequent methylated locus was SFRP2 followed by MGMT-B (81.2 and 66.6 percent respectively). Serologic detection of hypermethylation was 95% sensitive as compared with polyp tissue. No hypermethylation was detected in normal tissue and serum and its detection in patients with polyps, especially of serrated type, was specific. Conclusions: Serologic investigation for detection of MGMT-B, SFRP2 hypermethylation could facilitate prioritization of high risk patients for colonoscopic polyp detection and excision.