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Öğe Constitutive mismatch repair defect syndrome: New insights from whole exome sequencing data and functional studies(ELSEVIER SCIENCE BV, 2016) Caglayan, Ahmet Okay; Omay, Zeynep E. Erson; Koksal, Yavuz; Coskun, Suleyman; Unal, Ekrem; Per, Huseyin; Bilguvar, Kaya[Abstract not Available]Öğe Detection of p16 promotor hypermethylation in "Maras powder" and tobacco users(ELSEVIER SCI LTD, 2009) Saatci, Cetin; Caglayan, Ahmet Okay; Ozkul, Yusuf; Tahiri, Serpil; Turhan, Ahmet Bulent; Dundar, MunisBackground: A plant powder called "Maras powder" is widely used instead of cigarette smoking in the South-Eastern region of Turkey. It has been confirmed that this powder comprises tobacco Nicotiana rustica L. Methods: The aim of this study was to assess the effect of Maras powder and cigarette smoking on the PIS promotor hypermethylation. Twenty-two Maras powder users (Group I), 12 cigarette smokers (Group II), and 16 healthy controls who neither smoked nor used Maras powder (Group III)were included in the study. Hypermethylation of the P16 gene was examined using methylation-specific PCR (MSP) method in the blood of the three groups. Results: Aberrant PIS methylation was found in 7 of the 22 (31.8%) in Group I, in 3 of 12 (25%) in Group II, and in 1 of 16 (6.25%) in Group III. Conclusion: Maras powder may be as harmful as cigarette smoking, leading to hypermethylation in PIS and warrants detailed studies on this subject. (C) 2009 Elsevier Ltd. All rights reserved.Öğe The effect of maras powder on DNA methylation and micronucleus formation in human buccal tissue(TAYLOR & FRANCIS INC, 2008) Saatci, Cetin; Ozkul, Yusuf; Tahiri, Serpil; Caglayan, Ahmet Okay; Turhan, Ahmet Bulent; Dundar, MunisThe plant powder "maras powder" (MP) has been used widely instead of cigarettes in the southeastern region of Turkey. The aim of this study was to assess the impacts of MP and cigarette smoking on the methylation and micronuclei (MN) formation in buccal cells of humans with a comparison to blood lymphocytes. DNA samples from 80 subjects (40 MP users, 20 tobacco smokers, 20 healthy volunteers) were analyzed for their genomic methylation status using Hpa II and Msp I digestions followed by a simple gel electrophoresis and ethidium bromide staining. A densitometric method was developed to measure the methylation in genomic DNA samples and the results were evaluated using a software program designed for this purpose. Buccal epithelial cells were collected from the same groups and examined for MN formation. The results indicated that a general genomic hypomethylation was present in almost all of the samples that were obtained from MP users and tobacco smokers. This hypomethylation was significant in MP users compared to smokers and healthy volunteers. The percentage of cells containing MN was 1.93 in MP users, 0.95 in healthy volunteers, and 1.82 in smokers. The MN frequency was significantly higher in MP users and smokers than in healthy volunteers. There was no statistical difference between smokers and MP users. Evidence indicates that MP usage induces DNA hypomethylation and increase frequency of MN formation.Öğe Somatic POLE mutations cause an ultramutated giant cell high-grade glioma subtype with better prognosis(OXFORD UNIV PRESS INC, 2015) Erson-Omay, E. Zeynep; Caglayan, Ahmet Okay; Schultz, Nikolaus; Weinhold, Nils; Omay, S. Bulent; Ozduman, Koray; Koksal, YavuzBackground. Malignant high-grade gliomas (HGGs), including the most aggressive form, glioblastoma multiforme, show significant clinical and genomic heterogeneity. Despite recent advances, the overall survival of HGGs and their response to treatment remain poor. In order to gain further insight into disease pathophysiology by correlating genomic landscape with clinical behavior, thereby identifying distinct HGG molecular subgroups associated with improved prognosis, we performed a comprehensive genomic analysis. Methods. We analyzed and compared 720 exome-sequenced gliomas (136 from Yale, 584 from The Cancer Genome Atlas) based on their genomic, histological, and clinical features. Results. We identified a subgroup of HGGs (6 total, 4 adults and 2 children) that harbored a statistically significantly increased number of somatic mutations (mean = 9257.3 vs 76.2, P = .002). All of these "ultramutated" tumors harbored somatic mutations in the exonuclease domain of the polymerase epsilon gene (POLE), displaying a distinctive genetic profile, characterized by genomic stability and increased C-to-A transversions. Histologically, they all harbored multinucleated giant or bizarre cells, some with predominant infiltrating immune cells. One adult and both pediatric patients carried homozygous germline mutations in the mutS homolog 6 (MSH6) gene. In adults, POLE mutations were observed in patients younger than 40 years and were associated with a longer progression-free survival. Conclusions. We identified a genomically, histologically, and clinically distinct subgroup of HGGs that harbored somatic POLE mutations and carried an improved prognosis. Identification of distinctive molecular and pathological HGG phenotypes has implications not only for improved classification but also for potential targeted treatments.
