• 대한생식의학회:학술대회논문집
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• 대한불임학회 1996년도 추계 학술대회 및 정기총회
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• pp.49-49
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• 1996

• Journal of Genetic Medicine
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• 제15권2호
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• pp.87-91
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• 2018

X-linked dominant mutations in lysosome-associated membrane protein 2 (LAMP2) gene have been shown to be the cause of Danon disease, which is a rare disease associated with clinical triad of cardiomyopathy, skeletal myopathy, and mental retardation. Cardiac involvement is a common manifestation and is the leading cause of death in Danon disease. We report a case of a 24-month-old boy with hemizygous LAMP2 mutation who presented with failure to thrive and early-onset hypertrophic cardiomyopathy. We applied targeted exome sequencing and found a novel hemizygous c.692del variant in exon 5 of the LAMP2 gene, resulting a frameshift mutation p.Thr231Ilefs*11. Our study indicates that target next-generation sequencing can be used as a fast and highly sensitive screening method for inherited cardiomyopathy.

• Genomics & Informatics
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• 제12권2호
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• pp.50-57
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• 2014

We present a new next-generation sequencing-based method to identify somatic mutations of lung cancer. It is a comprehensive mutation profiling protocol to detect somatic mutations in 30 genes found frequently in lung adenocarcinoma. The total length of the target regions is 107 kb, and a capture assay was designed to cover 99% of it. This method exhibited about 97% mean coverage at $30{\times}$ sequencing depth and 42% average specificity when sequencing of more than 3.25 Gb was carried out for the normal sample. We discovered 513 variations from targeted exome sequencing of lung cancer cells, which is 3.9-fold higher than in the normal sample. The variations in cancer cells included previously reported somatic mutations in the COSMIC database, such as variations in TP53, KRAS, and STK11 of sample H-23 and in EGFR of sample H-1650, especially with more than $1,000{\times}$ coverage. Among the somatic mutations, up to 91% of single nucleotide polymorphisms from the two cancer samples were validated by DNA microarray-based genotyping. Our results demonstrated the feasibility of high-throughput mutation profiling with lung adenocarcinoma samples, and the profiling method can be used as a robust and effective protocol for somatic variant screening.

• 대한두경부종양학회지
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• 제37권2호
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• pp.1-9
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• 2021

Thyroid cancer refers to various cancers arising from thyroid gland. Differentiated thyroid cancers (DTCs) include papillary, follicular, and Hurthle cell carcinomas and represent cancers retain normal thyroid functions such as iodine uptake. Radioactive iodine (RAI) is generally used for upfront treatment of metastatic DTCs, but RAI refractory DTCs remain to be clinical challenges. Sorafenib and lenvatinib were approved for the treatment of RAI refractory DTCs and more recently, genomics-based targeted therapies have been developed for NTRK and RET gene fusion-positive DTCs. Poorly differentiated and anaplastic thyroid cancers (ATCs) are extremely challenging diseases with aggressive courses. BRAF/MEK inhibition has been proven to be highly effective in BRAF V600E mutation-positive ATCs and immune checkpoint inhibitors have shown promising activities. Medullary thyroid cancers, which arise from parafollicular cells of thyroid, represent a unique subset of thyroid cancer and mainly driven by RET mutation. In addition to vandetanib and cabozantinib, highly specific RET inhibitors such as selpercatinib and pralsetinib have demonstrated impressive activity and are in clinical use.

• KSII Transactions on Internet and Information Systems (TIIS)
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• 제15권8호
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• pp.2805-2826
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• 2021

In most cases, the routing policy of networks shows a preference for a static one-to-one mapping of communication pairs to routing paths, which offers adversaries a great advantage to conduct thorough reconnaissance and organize an effective attack in a stress-free manner. With the evolution of network intelligence, some flexible and adaptive routing policies have already proposed to intensify the network defender to turn the situation. Routing mutation is an effective strategy that can invalidate the unvarying nature of routing information that attackers have collected from exploiting the static configuration of the network. However, three constraints execute press on routing mutation deployment in practical: insufficient route mutation space, expensive control costs, and incompatibility. To enhance the availability of route mutation, we propose an OpenFlow-based route mutation technique called Polymorphic Path Transferring (PPT), which adopts a physical and virtual path segment mixed construction technique to enlarge the routing path space for elevating the security of communication. Based on the Markov Decision Process, with considering flows distribution in the network, the PPT adopts an evolution routing path scheduling algorithm with a segment path update strategy, which relieves the press on the overhead of control and incompatibility. Our analysis demonstrates that PPT can secure data delivery in the worst network environment while countering sophisticated attacks in an evasion-free manner (e.g., advanced persistent threat). Case study and experiment results show its effectiveness in proactively defending against targeted attacks and its advantage compared with previous route mutation methods.

• Annals of Pediatric Endocrinology and Metabolism
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• 제23권4호
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• pp.229-234
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• 2018

X-linked hypophosphatemic rickets is caused by loss-of-function mutations in PHEX, which encodes a phosphate-regulating endopeptidase homolog. We report a 26-year-old man with X-linked hypophosphatemic rickets who showed decreased serum phosphate accompanied by bilateral genu valgum and short stature. He had received medical treatment with vitamin D (alfacalcidol) and phosphate from the age of 3 to 20 years. He underwent surgery due to valgus deformity at the age of 14 and 15. Targeted gene panel sequencing for Mendelian genes identified a nonsense mutation in PHEX (c.589C>T; p.Gln197Ter) and a mosaic pattern where only 38% of sequence reads showed the variant allele. This mutation was not found in his mother, who had a normal phenotype. This is a case of a sporadic nonsense mutation in PHEX and up to date, this is the first case of a mosaic mutation in PHEX in Korea.

• Genomics & Informatics
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• 제15권1호
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• pp.48-50
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• 2017

Tumor tissues from biopsies or surgery are major sources for the next generation sequencing (NGS) study, but these procedures are invasive and have limitation to overcome intratumor heterogeneity. Recent studies have shown that driver alterations in tumor tissues can be detected by liquid biopsy which is a less invasive technique capable of both capturing the tumor heterogeneity and overcoming the difficulty in tissue sampling. However, it is still unclear whether the driver alterations in liquid biopsy can be detected by targeted NGS and how those related to the tissue biopsy. In this study, we performed whole-exome sequencing for a breast cancer tissue and identified PTEN p.H259fs*7 frameshift mutation. In the plasma DNA (liquid biopsy) analysis by targeted NGS, the same variant initially identified in the tumor tissue was also detected with low variant allele frequency. This mutation was subsequently validated by digital polymerase chain reaction in liquid biopsy. Our result confirm that driver alterations identified in the tumor tissue were detected in liquid biopsy by targeted NGS as well, and suggest that a higher depth of sequencing coverage is needed for detection of genomic alterations in a liquid biopsy.

• BMB Reports
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• 제53권7호
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• pp.341-348
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• 2020

The targeted nuclease clustered, regularly interspaced short palindromic repeats/CRISPR-associated proteins (CRISPR/Cas) system has recently emerged as a prominent gene manipulation method. Because of its ease in programming targeted DNA/protein binding through RNA in a vast range of organisms, this prokaryotic defense system is a versatile tool with many applications in the research field as well as high potential in agricultural and clinical improvements. This review will present a brief history that led to its discovery and adaptation. We also present some of its restrictions, and modifications that have been performed to overcome such restrictions, focusing specifically on the most common CRISPR/Cas9 mediated non-homologous end joint repair.

• Asian Pacific Journal of Cancer Prevention
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• 제15권8호
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• pp.3451-3455
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• 2014

Background: The serum carcinoembryonic antigen (CEA) level can reflect tumor growth, recurrence and metastasis. It has been reported that epidermal growth factor receptor (EGFR) mutations in exons 19 and 21may have an important relationship with tumor cell sensitivity to EGFR-TKI therapy. In this study, we investigated the clinical value of EGFR mutations and serum CEA in patients with non-small cell lung cancer (NSCLC). Materials and Methods: The presence of mutations in EGFR exons 19 and 21 in the tissue samples of 315 patients with NSCLC was detected with real-time fluorescent PCR technology, while the serum CEA level in cases who had not yet undergone surgery, radiotherapy, chemotherapy and targeted therapy were assessed by electrochemical luminescence. Results: The mutation rates in EGFR exons 19 and 21 were 23.2% and 14.9%, respectively, with the two combined in 3.81%. Measured prior to the start of surgery, radiotherapy, chemotherapy and targeted treatment, serum CEA levels were abnormally high in 54.3% of the patients. In those with a serum CEA level <5 ng/mL, the EGFR mutation rate was 18.8%, while with 5~19 ng/mL and ${\geq}20ng/mL$, the rates were 36.4% and 62.5%. In addition, in the cohort of patients with the CEA level being 20~49 ng/mL, the EGFR mutation rate was 85.7%, while in those with the CEA level ${\geq}50ng/mL$, the EGFR mutation rate was only 20.0%, approximately the same as in cases with the CEA level<5 ng/mL. Conclusions: There is a positive correlation between serum CEA expression level and EGFR mutation status in NSCLC patients, namely the EGFR mutation-positive rate increases as the serum CEA expression level rises within a certain range (${\geq}20ng/mL$, especially 20~49 ng/mL). If patient samples are not suitable for EGFR mutation testing, or cannot be obtained at all, testing serum CEA levels might be a simple and easy screening method. Hence, for the NSCLC patients with high serum CEA level (${\geq}20ng/mL$, especially 20~49 ng/mL), it is worthy of attempting EGFR-TKI treatment, which may achieve better clinical efficacy and quality of life.

• Asian Pacific Journal of Cancer Prevention
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• 제17권3호
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• pp.965-971
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• 2016

Aims: To investigate the distribution of epidermal growth factor receptor (EGFR) mutations, and explore any relationships with clinical characteristics in non-small-cell lung carcinoma (NSCLC) patients. Materials and Methods: EGFR mutations were assessed by ADx-ARMS in 261 NSCLC patients from West China Hospital of Sichuan University. Relationships between EGFR mutation and clinical characteristics were analyzed by SPSS. Results: The EGFR mutation rate was 48.7% (127/261), 19-del and L858R mutations occurred predominantly, accounting for 33.1% and 40.9%, respectively, in mutated cases. Moreover, 10.2% patients were found to carry double mutations. EGFR mutations occurred more frequently in women (57.5%) than in men (41.8%) (P=0.01), and were more frequent in non-smokers (61.2%) than in former or current smokers (31.2%) (P<0.00). In addition, they were more common in adenocarcinomas (52.8%) and adenosquamous carcinomas (42.8%) than in squamous cell carcinomas (14.8%) (p<0.00). However, only smoking history and pathological types, rather than gender, proved to be associated with EGFR mutations on multivariate logistic regression analysis. No significant differences in pathological stage and metastasis status were found between EGFR wild-type and mutated cases, although EGFR mutation type was related to pathological type (p=0.00) - 19-del, L858R and other mutation types respectively occurred in 34.2%, 42.5% and 23.3% of adenocarcinomas, but in 14.3%, 0% and 85.7% of non-adenocarcinomas. Conclusions: The EGFR mutation rate was 48.7% in NSCLCs in Southwest China, so that nearly 40% patients might benefit from targeted therapies. Smoking status and pathological types were independent predictors of EGFR mutation, while EGFR mutation type was related to only pathological type, rather than smoking status.