• Asian Pacific Journal of Cancer Prevention
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• v.16 no.8
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• pp.3523-3525
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• 2015

Gastric cancer is the second most common cause of cancer death worldwide. Environmental as well as genetic factors have been shown to be involved in its genesis. Among genetic factors, loss of function of a tumor suppressive gene named promyelocytic leukemia (PML) has been demonstrated in gastric cancer. In order to cast light in the mechanism by which PML protein is under-expressed in gastric cancer cells, we analyzed all exons and intron-exon boundaries of PML gene in 50 formalin-fixed paraffin-embedded tissue blocks from gastric carcinoma tumors by means of PCR-SSCP and CSGE, with direct sequencing of abnormally shifted bands. We found a novel sequence variant of unknown significance localized in intron 5 in 3 samples (c.1398+84delA). We did not detect any deleterious mutations of the PML gene. This study shows that PML mutations may not contribute to gastric adenocarcinoma development. Post-translational modifications or protein degradation might be mechanisms by which PML is not expressed in gastric tumors.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7261-7264
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• 2013

Recent genome wide sequencing has identified mutations in IDH1/IDH2 predominantly in grade II-III gliomas and secondary glioblastomas which are associated with favorable clinical outcome. These mutations have become molecular markers of significant diagnostic and prognostic relevance in the assessment of human gliomas. In the current study we evaluated IDH1 (R132) and IDH2 (R172) in 32 gliomas of various grades and tumor subtypes. Sequencing analysis revealed R132H mutations in 18.7% tumors, while none of the cases showed IDH2 (R172) mutations. The frequency of IDH1 mutations was higher in females (21.4%) than males (11.1%), and it was significantly higher in younger patients. Histological analyses demonstrated presence of necrosis and micro vascular proliferation in 69% and 75% respectively. Interestingly, IDH1 mutations were predominantly present in non-necrotic tumors as well as in cases showing microvascular proliferation. Of the six IDH1 positive cases, three were glioblastomas (IV), and one each were anaplastic oligoastrocytoma (III), anaplastic oligodendroglioma III (n=1) and diffuse astrocytoma. In conclusion, IDH1 mutations are quite frequent in Indian glioma patients while IDH2 mutations are not observed. Since IDH mutations are associated with good prognosis, their use in routine clinical practice will enable better risk stratification and management of glioma patients.

• Research in Plant Disease
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• v.25 no.1
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• pp.1-7
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• 2019

The rice blast fungus, Magnaporthe oryzae, is one of the most economically important crop diseases. In addition, rice-M. oryzae interaction is a classical gene-for-gene host-pathogen system. Race variation in pathogen groups was proposed as the main mechanism for rapid break-down of resistance in newly introduced rice cultivars. These new pathogen race variations may be caused by changes in an avirulence gene, such as (i) point mutations, (ii) insertion of transposons, and (iii) frame shifts. The avirulence gene AVR-Pita1 is representative avirulence gene in which all of these mutations are reported. In this review, we present a useful information for avirulence gene AVR-Pita1 and its homologous genes AVR-Pita2 and AVR-Pita3. We also review examples that cause mutations in these evolutionarily significant genes.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.2
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• pp.689-692
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• 2015

Background: Incorporation of molecular analysis of the epidermal growth factor receptor (EGFR) gene into routine clinical practice has shown great promise to provide personalized therapy of the non-small cell lung cancer (NSCLC) in the developed world. However, the genetic testing of EGFR mutations has not yet become routine clinical practice in territories remote from the central regions of Russia. Therefore, we aimed to study the frequency of major types of activating mutations of the EGFR gene in NSCLC patients residing in West Siberia. Materials and Methods: We examined EGFR mutations in exons 19 and 21 in 147 NSCLC patients (excluding squamous cell lung carcinomas) by real time polymerase chain reaction. Results: EGFR mutations were detected in 28 of the 147 (19%) patients. There were 19 (13%) cases with mutations in exon 19 and 9 cases (6%) in exon 21. Mutations were more frequently observed in women (42%, p=0.000) than in men (1%). A significantly higher incidence of EGFR mutations was observed in bronchioloalveolar carcinomas (28%, p=0.019) and in adenocarcinomas (21%, p=0.024) than in large cell carcinomas, mixed adenocarcinomas, and NOS (4%). The EGFR mutation rate was much higher in never-smokers than in smokers: 38% vs. 3% (p=0.000). The frequency of EGFR mutations in the Kemerovo and Tomsk regions was 19%. Conclusions: The incorporation of molecular analysis of the EGFR gene into routine clinical practice will allow clinicians to provide personalised therapy, resulting in a significant increase in survival rates and improvement in life quality of advanced NSCLC patients.

• Journal of Life Science
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• v.20 no.3
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• pp.453-456
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• 2010

Leukemia is the abnormal increase of hematopoietic progenitor cells in tissues, resulting in anemia, increased susceptibility to infection and impaired blood clotting. The adenosine deaminase (ADA) gene is an important druggable target for the treatment of leukemia patients. Genetic and molecular analyses were performed to determine the effects of ADA gene mutations in 20 leukemia patients in the Korean population. To analyze the relationship between genotype and phenotype, the ADA genomic DNAs - including 1,092 bp of 12 exons and partial intron sequences flanking each exon - were sequenced and compared. In this study, the known mutations in other diseases, more than 50 mutations already reported in patients with severe combined immunodeficiency disease (SCID) and autism, were not found, but two novel mutations in leukemia patients were discovered. They include one nonsense mutation (A>C at nt position 478, F101F) and one missense mutation (G>A at nt position 778, E260K). One missense mutation (G>A at nt position 22, D8Y) was also detected in 20 normal control patients (allelic frequency of 7.5%). Interestingly, subjects in the Korean population retained 2 bp insertion at the intron 6 (IVS6-52insGC), something that has never been shown in other populations. The genetic study to find out the correlation between the mutant alleles and leukemia patients revealed no association statistically (p>0.05). The mutation found in leukemia needs further study to determine its possibility as a molecular marker for the diagnosis of leukemia.

• Journal of Genetic Medicine
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• v.11 no.2
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• pp.63-68
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• 2014

Purpose: The mutation of the SLC26A4 gene is the second most common cause of congenital hearing loss after GJB2 mutations. It has been identified as a major cause of autosomal recessive nonsyndromic hearing loss associated with enlarged vestibular aqueduct and Pendred syndrome. Although most studies of SLC26A4 mutations have dealt with hearing-impaired patients, there are a few reports on the frequency of these mutations in the general population. The purpose of this study was to evaluate the prevalence of SLC26A4 mutations that cause inherited deafness in the general Korean population. Materials and Methods: We obtained blood samples from 144 Korean individuals with normal hearing. The samples were subjected to polymerase chain reaction to amplify the entire coding region of the SLC26A4 gene, followed by direct DNA sequencing. Results: Sequencing analysis of this gene identified 5 different variants (c.147C>G, c.225G>C, c.1723A>G, c.2168A>G, and c.2283A>G). The pathogenic mutation c.2168A>G (p.H723R) was identified in 1.39% (2/144) of the subjects with normal hearing. Conclusion: These data provide information about carrier frequency for SLC26A4 mutation-associated hearing loss and have important implications for genetic diagnostic testing for inherited deafness in the Korean population.

• Genomics & Informatics
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• v.21 no.3
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• pp.32.1-32.11
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• 2023

Resistance to anti-tuberculosis drugs, especially ethambutol (EMB), has been widely reported worldwide. EMB resistance is caused by mutations in the embB gene, which encodes the arabinosyl transferase enzyme. This study aimed to detect mutations in the embB gene of Mycobacterium tuberculosis from Papua and to evaluate their impact on the effectiveness of EMB. We analyzed 20 samples of M. tuberculosis culture that had undergone whole-genome sequencing, of which 19 samples were of sufficient quality for further bioinformatics analysis. Mutation analysis was performed using TBProfiler, which identified M306L, M306V, D1024N, and E378A mutations. In sample TB035, the M306L mutation was present along with E378A. The binding affinity of EMB to arabinosyl transferase was calculated using AutoDock Vina. The molecular docking results revealed that all mutants demonstrated an increased binding affinity to EMB compared to the native protein (-0.948 kcal/mol). The presence of the M306L mutation, when coexisting with E378A, resulted in a slight increase in binding affinity compared to the M306L mutation alone. The molecular dynamics simulation results indicated that the M306L, M306L + E378A, M306V, and E378A mutants decreased protein stability. Conversely, the D1024N mutant exhibited stability comparable to the native protein. In conclusion, this study suggests that the M306L, M306L + E378A, M306V, and E378A mutations may contribute to EMB resistance, while the D1024N mutation may be consistent with continued susceptibility to EMB.

• Animal cells and systems
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• v.15 no.4
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• pp.310-314
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• 2011

The Banna miniature pig (BNMP) is a representative miniature pig breed in China. Even though BNMP dwarfism is obvious, its underlying causative mutations remain unknown. In this study, the BNMP and Large White pig (LWP) serum growth hormone (GH) and insulin-like growth factor (IGF-1) levels were detected by ELISA and compared. BNMP serum IGF-1 levels were significantly lower than LWP levels (P<0.05). The miniature condition may arise from mutations in the GH and GH receptor (GHR) genes. Therefore, GH and GHR cDNA from the BNMP were cloned into a pMD18-T vector by RT-PCR using the total RNA obtained from the BNMP's pituitary and liver tissues. Sequencing results indicated that the open reading frame of the BNMP GH gene is composed of a 26-residue signal peptide and a 191-residue mature peptide. The coding sequence of the BNMP GHR gene contained 639 amino acids, including a signal peptide that is 18 amino acids long. Two amino acid substitutions, A09V and R22Q, were found in the signal peptide of the GH gene. Additionally, the S104P mutation was found in the BNMP's mature GH protein. Four mutations in the cytoplasmic domain of GHR may influence the downstream signal transduction of GHR, which needs further experimental evidence.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.11
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• pp.4521-4524
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• 2015

Background: Endometrial carcinoma is the most common malignant tumor of the female genital tract and the fourth most common cancer in Iranian women after breast, colorectal and lung cancers. Various genetic alterations appear to be early events in the pathogenesis of endometrial carcinoma and it seems that PTEN is the most commonly mutated gene in the endometrioid subtype. The aim of the present study was to investigate the correlation between mutations in exon 7 of PTEN gene and endometrial carcinoma. Materials and Methods: Seventy-five patients with endometrial carcinoma and 75 females whose underwent hysterectomy for non tumoral indication were selected for evaluation of PTEN mutations in exon 7 by PCR-SSCP and sequencing. Correlations between the frequency and type of mutation and the pathologic findings of the cancer (tumor subtype, stage and grade) were assessed. Results: All of the samples were obtained from Iranian patients. 60 % (45 cases) of the tumors were endometriod and 40% (30 cases) were of serous type. The grade distributions of the 75 cases according to the FIGO staging system were as follows: low grade, 20 cases; high grade 55 cases, low stage, 41 cases; high stage 34 cases. For exon 7 of the PTEN gene, the analysis showed that there were no mutations in our cases. Conclusions: Our findings in the present study suggest that exon 7 of PTEN does not play any significant role in the development of endometrial carcinoma in Iranian cases.

• Genomics & Informatics
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• v.14 no.3
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• pp.78-84
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• 2016

Extranodal natural killer (NK)/T-cell lymphoma, nasal type (NKTCL), is a malignant disorder of cytotoxic lymphocytes of NK or T cells. It is an aggressive neoplasm with a very poor prognosis. Although extranodal NKTCL reportedly has a strong association with Epstein-Barr virus, the molecular pathogenesis of NKTCL has been unexplored. The recent technological advancements in next-generation sequencing (NGS) have made DNA sequencing cost- and time-effective, with more reliable results. Using the Ion Proton Comprehensive Cancer Panel, we sequenced 409 cancer-related genes to identify somatic mutations in five NKTCL tissue samples. The sequencing analysis detected 25 mutations in 21 genes. Among them, KMT2D, a histone modification-related gene, was the most frequently mutated gene (four of the five cases). This result was consistent with recent NGS studies that have suggested KMT2D as a novel driver gene in NKTCL. Mutations were also found in ARID1A, a chromatin remodeling gene, and TP53, which also recurred in recent NGS studies. We also found mutations in 18 novel candidate genes, with molecular functions that were potentially implicated in cancer development. We suggest that these genes may result in multiple oncogenic events and may be used as potential bio-markers of NKTCL in the future.