• Journal of Gastric Cancer
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• v.3 no.4
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• pp.214-220
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• 2003

Purpose: The aim of this study was to investigate the frequency of loss of heterozygosity and the microsatellite instability at multiple tumor suppressor gene loci in gastric adenocarcinomas. Materials and Methods: Loss of heterozygosity and the microsatellite instability at several tumor suppressor gene loci were analyzed in 29 primary gastric carcinomas by using microdissection and the polymerase chain reaction. Results: Twenty-three ($79\%$) of the 29 cases demonstrated loss of heterozygosity at one or more loci. The frequency of loss of heterozygosity at the p53 locus was the highest ($63\%$) and those at the VHL, APC, p16, Rb, MEN1, BRCA1, DPC4, 3p21, and 16p13 region were $41\%,\;36\%,\;19\%,\;29\%,\;33\%,\;26\%,\;21\%,\;32\%,\;and\;11\%$, respectively. Compared with histological type, loss of heterozygosity was more common in diffuse-type gastric cancer (P<0.01). Interestingly, 9 of 10 tumors with allelic deletion at the p53 locus showed loss of heterozygosity at other tumor suppressor gene loci. The microsatellite instability was also detected in 6 ($20\%$) of the 29 cases at one or more loci. Conclusion: These data suggest that frequent loss of heterozygosity and the microsatellite instability at multiple tumor suppressor genes might be required for the development and the progression of gastric carcinomas and that p53 allelic loss may be the most frequent event in the development of gastric carcinomas.

• Korean Journal of Clinical Laboratory Science
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• v.40 no.1
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• pp.41-47
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• 2008

Colorectal carcinoma is occurred frequently to Korean and so ranked the fourth from various cancers. Due to western dietary life, this cancer has been increased continually. Therefore, the study will be needed to find a candidate gene involved in the development and progression of colorectal carcinoma and to diagnose and treatment helpfully. The striking feature from cancer suppressor genes is known for LOH (loss of heterozygosity), which is the method to find allele genetic loss or mutation of cancer cell. The purpose of this study was designed to find a carcinogenic gene from colon cancer using microsatellite marker on 17th and 18th chromosome from 30 subjects. The LOH was investigated in order of D18S59 57% (17/30), TP53CA 50% (15/30), D18S68 47% (14/30), D18S69 43% (13/30). The genetic mutation depends on loci of colorectal carcinoma was shown higher with 2.44 from colon cancer than with 1.25 from right colorectal carcinoma (p<0.032). The genetic mutation with lymph nodes was investigated higher with 2.69 at mutated group than with 1.14 at non-mutated group (p<0.003). At genetic mutated pattern depends on disease stage, there was higher significant difference at III-IV stage 2.50 than that of I-II stage 1.17, respectively (p=0.015). There was no difference at comparison between histological classification and serological CEA increase. The loss on 18q21 found in this study is highly recurrence loci and was observed 43% for Korean with high recurrence. Therefore, LOH is a very useful tool to detect 18q21 loci in clinical application, prior to the treatment of colorectal carcinoma. After the operation of colorectol carcinoma, the efficient application using LOH at operated part tissue which is designed to protect the recurrence as well as its cure will be needed.

• Journal of Gastric Cancer
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• v.4 no.2
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• pp.109-120
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• 2004

Purpose: Individual gastric cancers demonstrate complicated genetic alterations. The PCR-based analysis of polymorphic microsatellite sequences on cancer-related chromosomes has been used to detect chromosomal loss and microsatellite instability. For the purpose of preoperative usage, we analyzed the correspondance rate of the microsatellite genotype between endoscopic biopsy and surgical specimens. Materials and Methods: Seventy-three pairs of biopsy and surgical specimens were examined for loss of heterozygosity and microsatellite instability by using 40 microsatellite markers on eight chromosomes. Microsatellite alterations in tumor DNAs were classified into a high-risk group (baselinelevel loss of heterozygosity: 1 chromosomal loss in diffuse type and high-level loss of heterozygosity: 4 or more chromosomal losses) and a low-risk group (microsatellite instability and low-level loss of heterozygosity: 2 or 3 chromosomal losses in diffuse type or $1\∼3$ chromosomal losses in intestinal type) based on the extent of chromosomal loss and microsatellite instability. Results: The chromosomal losses of the biopsy and the surgical specimens were found to be different in 21 of the 73 cases, 19 cases of which were categorized into a genotype group of similar extent. In 100 surgical specimens, the high-risk genotype group showed a high incidence of nodal involvement (19 of 23 cases: $\leq$5 cm; 23 of 24 cases: >5 cm) irrespective of tumor size while the incidence of nodal involvement for the low-risk genotype group depended on tumor size (5 of 26 cases: $\leq$5 cm; 18 of 27 cases: >5 cm). Extraserosal invasion was more frequent in large-sized tumor in both the high-risk genotype group ($\leq$5 cm: 12 of 23 cases; >5 cm: 23 of 24 cases) and the low-risk genotype group ($\leq$5 cm: 7 of 26 cases; >5 cm: 16 of 27 cases). The preoperative prediction of tumor invasion and nodal involvement based on tumor size and genotype corresponded closely to the pathologic tumor stage (ROC area >0.7). Conclusion: An endoscopic biopsy specimen of gastric cancer can be used to make a preoperative genetic diagnosis that accurately reflect the genotype of the corresponding surgical specimen.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.6
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• pp.2489-2493
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• 2015

Background: Loss of heterozygosity (LOH) on chromosomal regions is crucial in tumor progression and this study aimed to identify genome-wide LOH in pancreatic cancer. Materials and Methods: Single-nucleotide polymorphism (SNP) profiling data GSE32682 of human pancreatic samples snap-frozen during surgery were downloaded from Gene Expression Omnibus database. Genotype console software was used to perform data processing. Candidate genes with LOH were screened based on the genotype calls, SNP loci of LOH and dbSNP database. Gene annotation was performed to identify the functions of candidate genes using NCBI (the National Center for Biotechnology Information) database, followed by Gene Ontology, INTERPRO, PFAM and SMART annotation and UCSC Genome Browser track to the unannotated genes using DAVID (the Database for Annotation, Visualization and Integration Discovery). Results: The candidate genes with LOH identified in this study were MCU, MICU1 and OIT3 on chromosome 10. MCU was found to encode a calcium transporter and MICU1 could encode an essential regulator of mitochondrial $Ca^{2+}$ uptake. OIT3 possibly correlated with calcium binding revealed by the annotation analyses and was regulated by a large number of transcription factors including STAT, SOX9, CREB, NF-kB, PPARG and p53. Conclusions: Global genomic analysis of SNPs identified MICU1, MCU and OIT3 with LOH on chromosome 10, implying involvement of these genes in progression of pancreatic cancer.

• Journal of Korean Neurosurgical Society
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• v.48 no.1
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• pp.14-19
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• 2010

Objective : Allelic losses or loss of heterozygosity (LOH) at many chromosomal loci have been found in the cells of meningiomas. The objective of this study was to evaluate LOH at several loci of different chromosomes (1p32, 17p13, 7q21, 7q31, and 22q13) in different grades of meningiomas. Methods : Forty surgical specimens were obtained and classified as benign, atypical, and anaplastic meningiomas. After DNA extraction, ten polymorphic microsatellite markers were used to detect LOH. Medical and surgical records, as well as pathologic findings, were reviewed retrospectively. Results : LOH at 1p32 was detected in 24%, 60%, and 60% in benign, atypical, and anaplastic meningiomas, respectively. Whereas LOH at 7q21 was found in only one atypical meningioma. LOH at 7q31 was found in one benign meningioma and one atypical meningioma. LOH at 17p13 was detected in 4%, 40%, and 80% in benign, atypical, and anaplastic meningiomas, respectively. LOH at 22q13 was seen in 48%, 60%, and 60% in benign, atypical, and anaplastic meningiomas, respectively. LOH results at 1p32 and 17p13 showed statistically significant differences between benign and non-benign meningiomas. Conclusion : LOH at 1p32 and 17p13 showed a strong correlation with tumor progression. On the other hand, LOH at 7q21 and 7q31 may not contribute to the development of the meningiomas.

• Genomics & Informatics
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• v.20 no.1
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• pp.4.1-4.8
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• 2022

Loss of heterozygosity (LOH) is a genomic aberration. In some cases, LOH can be generated without changing the copy number, which is called copy-neutral LOH (CN-LOH). CN-LOH frequently occurs in various human diseases, including cancer. However, the biological and clinical implications of CN-LOH for human diseases have not been well studied. In this study, we compared the performance of CN-LOH determination using three commonly used tools. For an objective comparison, we analyzed CN-LOH profiles from single-nucleotide polymorphism array data from 10 colon adenocarcinoma patients, which were used as the reference for comparison with the CN-LOHs obtained through whole-exome sequencing (WES) data of the same patients using three different analysis tools (FACETS, Nexus, and Sequenza). The majority of the CN-LOHs identified from the WES data were consistent with the reference data. However, some of the CN-LOHs identified from the WES data were not consistent between the three tools, and the consistency with the reference CN-LOH profile was also different. The Jaccard index of the CN-LOHs using FACETS (0.84 ± 0.29; mean value, 0.73) was significantly higher than that of Nexus (0.55 ± 0.29; mean value, 0.50; p = 0.02) or Sequenza (0 ± 0.41; mean value, 0.34; p = 0.04). FACETS showed the highest area under the curve value. Taken together, of the three CN-LOH analysis tools, FACETS showed the best performance in identifying CN-LOHs from The Cancer Genome Atlas colon adenocarcinoma WES data. Our results will be helpful in exploring the biological or clinical implications of CN-LOH for human diseases.

• Korean Journal of Head & Neck Oncology
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• v.14 no.1
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• pp.20-26
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• 1998

Objectives: Deletion in the short arm of chromosome 3 is common in many human cancers, including sporadic and hereditary renal carcinomas, small cell lung carcinomas, non-small cell lung carcinomas, and carcinomas of the ovary, breast, and cervix. A high frequency of chromosomal aberrations in head and neck cancers involving chromosome 3p has also been reported. These findings suggest that multiple tumor suppressor genes may be present on the short arm of chromosome 3. Materials and Methods: To investigate the possibility of chromosome 3p deletions in the Korean head and neck cancer patients, we applied a polymerase chain reaction(PCR)-based Restriction Fragment Length Polymorphism analysis to the DNA samples of matched normal mucosa and head and neck squamous cell carcinomas from 19 patients. Results: In the 19 normal samples heterozygosity at the polymorphic loci varied: 6 at the D3F15S2 locus(on telomeric 3p21), 2 at the D3S32 locus(on centromeric 3p21), and 4 at the THRB locus(on centromeric 3p24). In 12 matched carcinoma specimens, LOH(loss of heterozygosity) was observed at D3F15S2 in 1 of 6(17%), D3S32 in 1 of 2(50%), and at THRB in 2 of 4 cases(50%). Conclusion: The frequency of chromosome 3p deletion in the Korean head and neck carcinomas appear as other country did.

• Asian-Australasian Journal of Animal Sciences
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• v.33 no.1
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• pp.12-23
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• 2020

Objective: The objective of a conservation program is to maintain maximum genetic diversity and preserve the viability of a breed. However, the efficiency of a program is influenced by the ability to accurately measure and predict genetic diversity. Methods: To examine this question, we conducted a simulation in which common measures (i.e. heterozygosity) and novel measures (identity-by-descent probabilities and parental genomic components) were used to estimate genetic diversity within a conserved population using double-labeled single nucleotide polymorphism markers. Results: The results showed that the accuracy and sensitivity of identity-by-state probabilities and heterozygosity were close to identity by descent (IBD) probabilities, which reflect the true genetic diversity. Expected heterozygosity most closely aligned with IBD. All common measures suggested that practices used in the current Chinese pig conservation program result in a ~5% loss in genetic diversity every 10 generations. Parental genomic components were also analyzed to monitor real-time changes in genomic components for each male and female ancestor. The analysis showed that ~7.5% of male families and ~30% of female families were lost every 5 generations. After 50 generations of simulated conservation, 4 male families lost ~50% of their initial genomic components, and the genomic components for 24.8% of the female families were lost entirely. Conclusion: In summary, compared with the true genetic diversity value obtained using double-labeled markers, expected heterozygosity appears to be the optimal indicator. Parental genomic components analysis provides a more detailed picture of genetic diversity and can be used to guide conservation management practices.

• Genomics & Informatics
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• v.11 no.1
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• pp.24-33
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• 2013

We had analyzed 10 exome sequencing data and single nucleotide polymorphism chips for blood cancer provided by the PGM21 (The National Project for Personalized Genomic Medicine) Award program. We had removed sample G06 because the pair is not correct and G10 because of possible contamination. In-house software somatic copy-number and heterozygosity alteration estimation (SCHALE) was used to detect one loss of heterozygosity region in G05. We had discovered 27 functionally important mutations. Network and pathway analyses gave us clues that NPM1, GATA2, and CEBPA were major driver genes. By comparing with previous somatic mutation profiles, we had concluded that the provided data originated from acute myeloid leukemia. Protein structure modeling showed that somatic mutations in IDH2, RASGEF1B, and MSH4 can affect protein structures.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.37 no.6
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• pp.550-555
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• 2011

Chromosomal loss of heterozygosity (LOH) is a common mechanism for the inactivation of tumor suppressor genes in human epithelial cancers. LOH patterns can be generated through allelotyping using polymorphic microsatellite markers; however, owing to the limited number of available microsatellite markers and the requirement for large amounts of DNA, only a modest number of microsatellite markers can be screened. Hybridization to single nucleotide polymorphism (SNP) arrays using Affymetarix GeneChip Mapping 10 K 2.0 Array is an efficient method to detect genome-wide cancer LOH. We determined the presence of LOH in oral SCCs using these arrays. DNA was extracted from tissue samples obtained from 10 patients with tongue SCCs who presented at the Hospital of Tokyo Dental College. We examined the presence of LOH in 3 of the 10 patients using these arrays. At the locus that had LOH, we examined the presence of LOH using microsatellite markers. LOH analysis using Affymetarix GeneChip Mapping 10K Array showed LOH in all patients at the 1q31.1. The LOH regions were detected and demarcated by the copy number 1 with the series of three SNP probes. LOH analysis of 1q31.1 using microsatellite markers (D1S1189, D1S2151, D1S2595) showed LOH in all 10 patients (100). Our data may suggest that a putative tumor suppressor gene is located at the 1q31.1 region. Inactivation of such a gene may play a role in tongue tumorigenesis.