• Asian Pacific Journal of Cancer Prevention
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• v.16 no.13
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• pp.5211-5217
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• 2015

Background: We earlier used PCR-dHPLC for mutation analysis of BRCA1 and BRCA2. In this article we report application of targeted resequencing of 30 genes involved in hereditary cancers. Materials and Methods: A total of 91 patient samples were analysed using a panel of 30 genes in the Illumina HiScan SQ system. CLCBio was used for mapping reads to the reference sequences as well as for quality-based variant detection. All the deleterious mutations were then reconfirmed using Sanger sequencing. Kaplan Meier analysis was conducted to assess the effect of deleterious mutations on disease free and overall survival. Results: Seventy four of the 91 samples had been run earlier using the PCR-dHPLC and no deleterious mutations had been detected while 17 samples were tested for the first time. A total of 24 deleterious mutations were detected, 11 in BRCA1, 4 in BRCA2, 5 in p53, one each in RAD50, RAD52, ATM and TP53BP1. Some 19 deleterious mutations were seen in patients who had been tested earlier with PCR-dHPLC [19/74] and 5/17 in the samples tested for the first time, Together with our earlier detected 21 deleterious mutations in BRCA1 and BRCA2, we now had 45 mutations in 44 patients. BRCA1c.68_69delAG;p.Glu23ValfsX16 mutation was the most common, seen in 10/44 patients. Kaplan Meier survival analysis did not show any difference in disease free and overall survival in the patients with and without deleterious mutations. Conclusions: The NGS platform is more sensitive and cost effective in detecting mutations in genes involved in hereditary breast and/or ovarian cancers.

• Korean Journal of Head & Neck Oncology
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• v.22 no.1
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• pp.8-14
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• 2006

Objectives: The p53 tumor suppressor gene has a key role in cellular control mechanisms involving apoptosis and DNA repair, leading to the G1 arrest following DNA damage. Its mutation is one of the most frequent alterations in human cancers. Ki-67 is identified in replicating cells of both benign and malignant lesions, so it can be the predictor of proliferative activity. The aim of this study is to evaluate the expression of p53 and Ki-67 in salivary gland tumors. Materials and Methods: Immunohistochemical analysis was used to detect expression of p53 and Ki-67 in paraffin-embedded samples from 31 benign and 27 malignant salivary gland tumors. Results were analyzed between benign and malignant tumors and compared with the clinical parameters such as stage and recurrence in malignant tumors. Results: p53 overexpression was detected in 19.6% of benign tumors and 40.7% of malignant tumors, but there was no statistical significance. p53 was significantly expressed in Warthin's tumor(45.5%) compared with pleomorphic adenoma(5.9%). Only 5.9% of pleomorphic adenoma were positive for p53, while 60% of carcinoma ex pleomorphic adenoma were positive for p53. Ki-67 was expressed in 3.2% of benign tumors and 51.9% of malignant tumors, which showed significant higher expression in malignant tumors. In malignant tumors, p53 and Ki-67 expressions bore no correlation to stage and recurrence. Conclusion: p53 overexpression is not associated with the progression of malignant tumors, and Ki-67 overexpression can be used as biologic indicator of malignant salivary gland tumors.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.150-151
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• 2003

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the progressive deterioration of cognition and memory in association with widespread neuronal loss. AD is supposed to be very often associated with missense mutation located on homologous protein Presenilin (PS1) and (PS2). Up to now, the molecular mechanisms underlying the role of the gene mutation in AD still remain unclear. (omitted)

• The Journal of the Korean bone and joint tumor society
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• v.20 no.2
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• pp.99-103
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• 2014

Li-Fraumeni syndrome (LFS) is an autosomal dominant hereditary disorder characterised by a variety of different tumor types in children and young adults. That contains with a germline mutation in the tumor suppressor gene Tumor Protein p53 (TP53). That is extremely rare. Furthermore, this is sometimes overlooked. Here, we report a case of LFS which was confirmed by mutational analysis of the p53 gene. Also, literature review is intended to improve understanding of this disease entity.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5535-5538
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• 2012

Background: There have been case reports of oral squamous cell carcinoma arising from gingival overgrowth induced by phenytoin - an antiepileptic drug. However, a detailed analysis for the presence of mutations in p53 and ras genes, which are the two most frequently mutated genes in cancers, in phenytoin induced gingival overgrowth tissues has hitherto not been performed. Methods: Cellular DNA isolated from twenty gingival overgrowth tissues collected from patients undergoing phenytoin therapy were amplified using primers for p53 (exons 5-8) and H-ras (exons 1-2) genes. The PCR amplicons were then gel purified and subjected to direct sequencing analysis to screen for mutations. Results: Direct sequencing of twenty samples of phenytoin induced gingival growth did not identify mutations in any of the exons of p53 and H-ras genes that were analyzed. Conclusion: Our result indicates that mutational alteration of p53 and H-ras genes is infrequent in phenytoin induced gingival growth, which thus suggests a non malignant nature of this pathology. The findings in the present study are clinically significant as a large number of epileptic patients are treated with phenytoin.

• 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.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.6013-6017
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• 2013

Background: To evaluate the clinicopathologic and demographic characteristics of triple-negative breast cancer (TNBC) patients and to determine differences from non-triple-negative cases. Materials and Methods: A detailed review of the medical records of 882 breast cancer (BC) patients was conducted to obtain information regarding age, menopausal status, height and weight at the time of diagnosis, presence of diabetes or hypertension, and pathologic characteristics of the tumor (tumor size, lymph node status, histologic grade, ER status, PR status, HER2 status, p53 mutation). Body mass index (BMI) was calculated and a value of ${\geq}30$ was considered as indicative of obesity. Results: 14.9% (n=132) of the patients had TNBC. There was no difference among the patients in terms of median age, comorbid conditions and menopausal status. The proportion of medullary, tubular and mucinous carcinomas was significantly higher (15.9%) in the triple-negative (TN) group, while invasive lobular histology was more frequent (8.2%) among non-triple negative (NTN) cases (p<0.001). Grade 3 (G3) tumors were more frequent in the triple-negative group (p<0.001). The rate of p53 mutation was 44.3% in TN tumors versus 28.2% in the NTN group (p<0.001). The two groups were similar in terms of LN metastasis. In the NTN group, the rate of patients with BMI ${\geq}30$ was 53% among postmenopausal patients, while it was 36% among premenopausal women, and the difference was statistically significant (p<0.001). No significant difference was observed in terms of BMI between postmenopausal and premenopausal patients in the TN group (p=0.08). Conclusions: TNBC rates and clinicopathologic characteristics of the Turkish patient population were consistent with the data from Europe and America. However, no relationship between obesity and TNBC was observed in our study. The association between TNBC and obesity needs to be evaluated in a larger patient population.

• Journal of Chest Surgery
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• v.32 no.8
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• pp.726-731
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• 1999

Background: The distinction between non-invasive and invasive or thymic carcinoma has been severely compromised by lack of objective morphological criteria. A reliable biological marker of tumor aggressiveness is, therefore, mandatory for predicting tumor behavior. Material and Method: Thirty thymic epithelial tumors, including 7 non-invasive thymoma, 10 invasive thymoma, and 13 thymic carcinoma of the Rosai's classification; and 5 stage I, 7 stage II, 2 stage III, and 3 stage IVa of the Masaoka stage of thymoma were investigated for expression of bcl-2 and p53 proteins by immunohistochemistry. Result: The thymic epithelial cells showed positive immunostain for bcl-2 in 0 (0%), 3 (30%), 8 (61.5%) of categories in the Rosai's classification respectively and in 0 (0%), 1 (14.3%), 2 (100%), 0 (0%) of stage I, II, III, IVa of the Masaoka stage respectively. Thymic carcinoma, and high stage thymoma had significantly higher proportion of bcl-2 expression than thymoma (p=0.021) and low stage thymoma (p=0.011). However, p53 showed no correlation with the histological subtypes nor with clinical aggressiveness. Bcl-2 expression appeared to be positively correlated with p53 immunoactivity (p=0.007, kappa=0.525). Conclusion: These date indicate that bcl-2 expression correlates with aggressiveness in thymic epithelial tumors, but further studies on mutation of p53 protein is necessary because bcl-2 expression appeared to be positively correlated with p53 immunoactivity.

• BLOOD RESEARCH
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• v.53 no.4
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• pp.294-298
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• 2018

Background Production of immunosuppressive enzymes such as indoleamine 2,3-dioxygenase (IDO) is one of the strategies employed by hematologic malignancies, including acute myeloid leukemia (AML), to circumvent immune surveillance. Moreover, IDO has the ability to convert $CD4^+CD25^-$ conventional T cells into regulatory T cells (Tregs). In this study, we evaluated the expression of IDO in cytogenetically normal acute myeloid leukemia (CN-AML) patients and its correlation with the Treg marker, FOXP3, as well as clinical and laboratory parameters. Methods Thirty-seven newly diagnosed CN-AML patients were enrolled in our study along with 22 healthy individuals. The expression of the IDO and FOXP3 genes was analyzed by SYBR Green real-time PCR. Results Both IDO and FOXP3 were highly upregulated in CN-AML patients compared to control groups (P=0.004 and P=0.031, respectively). A positive correlation was observed between IDO and FOXP3 expression among AML patients (r=0.512, P=0.001). Expression of IDO and FOXP3 showed no significant correlation with laboratory parameters such as white blood cell and platelet counts, hemoglobin levels, bone marrow blast percentage, gender, and FLT3 mutation status (P>0.05). Conclusion Higher IDO expression in CN-AML patients may be associated with an increased Treg phenotype which may promote disease progression and lead to poor prognosis of CN-AML patients.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.17 no.1
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• pp.11-17
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• 2017

Purpose: Phenylketonuria (PKU) results from a deficiency of phenylalanine hydroxylase (PAH). The mutation of the PAH gene results in decreased phenylalanine hydroxylase enzyme activity in hyperphenylalaninemia (HPA) patients. This study reports ten cases of patients with the benign HPA genotype c.158G>A (p.Arg53His, R53H) variant in the PAH gene and aims to evaluate the clinical significance of the R53H variant. Methods: Ten Korean patients with the HPA genotype the R53H variant were included in this study. A retrospective medical record review was conducted. We characterized the phenotypes of the patients with HPA with the R53H variant using the following system: classic PKU, moderate PKU, mild PKU, Mild HPA, and benign HPA. Results: Five patients had the R53H variant with the "Pathogenic" variants (R413P, R241C, $Y356^*$, c.442-1G>A, $Y325^*$), Two patients had the "Likely pathogenic" variants ($W187^*$, A259T), Two patients had the "Uncertain significance" variants (R53H, G344D), and One patient had the "Not provided" variant (c.1066-14C>G). Nine patients genotyped with the R53H variant were the patient with benign HPA and One patient genotyped with the R53H homozygote was within normal range of plasma phenylalanine. None of the ten patients required dietary restriction of phenylalanine or pharmacotherapy to maintain their plasma phenylalanine levels and showed no clinical symptoms of HPA. Conclusion: Ten patients with HPA genotype the R53H variant were the patient with benign HPA and showed no clinical symptoms of HPA. Thus, the R53H variant, which was previously classified as an "Uncertain significance" mutation in HPA patients, should be re-classified as "Benign."