Gokhan Ozan Cetin

Dokuz Eylul University, Ismir, İzmir, Turkey

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Publications (11)17.97 Total impact

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    ABSTRACT: Myeloid differentiation primary response 88 (MYD88) is a common adaptor protein that is responsible for signaling from several receptors; mutations in this gene may play a role in the pathogenesis of lymphoma. We aimed to determine the MYD88 L265P mutation frequency, the level of MYD88 expression, and their associations with clinicopathological parameters in mature B-cell non-Hodgkin lymphomas (NHLs). A total of 68 patients were included in the study. The presence of the MYD88 L265P mutation was analyzed by real-time polymerase chain reaction and direct sequencing. MYD88 protein expression was evaluated by immunohistochemistry (IHC) using two different scoring systems. MYD88 L265P mutation was present in eight (18.6%) diffuse large B-cell lymphoma (DLBCL) patients. We also observed a significant association between the loss of MYD88 expression and advanced stage in both mature B-cell NHL and DLBCL according to the first IHC scoring systems (p=0.015 and p=0.024, respectively). An association was also seen between MYD88 overexpression and low clinical risk in both mature B-cell NHL and DLBCL according to the second IHC scoring system (p=0.027 and p=0.024, respectively). The L265P mutation may be helpful for understanding the pathogenesis of immune-privileged site-associated DLBCLs. The presence of the mutation, together with its protein overexpression, could also be used as a prognostic marker in advanced stage DLBCLs.
    Genetic Testing and Molecular Biomarkers 05/2015; 19(7). DOI:10.1089/gtmb.2015.0041 · 1.46 Impact Factor
  • Gokhan Ozan Cetin · Asli Toylu · Nese Atabey · Zeynep Sercan · Meral Sakizli ·
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    ABSTRACT: The Wnt planar cell polarity (PCP) pathway is one of the Wnt pathways which plays a critical role in cell proliferation and fate. The VANGL1 protein is one of Wnt-PCP pathway components. It is known that Wnt-PCP pathway has major roles in cell motility but its role in hepatocellular carcinoma (HCC) progression through invasion and metastasis needs to be clarified. We silenced VANGL1 gene expression in the HepG2 HCC cell line by stable transfection with a vector containing siRNA template for VANGL1 and investigated the change in cell invasion and motility. Transfected cells with the siRNA template showed significantly suppressed invasive capacity when compared to controls although cellular motility was only slightly affected. Our study showed a basal role for VANGL1 with respect to the invasive capacity of HCC cells. This suggests that the Wnt-PCP pathway may play a role in progression of HCC through cellular invasion but further studies are needed to clarify its role in cell motility.
    Genetic Testing and Molecular Biomarkers 04/2015; 19(6). DOI:10.1089/gtmb.2015.0014 · 1.46 Impact Factor
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    ABSTRACT: Aim: To assess the association between age-related macular degeneration (AMD) and three single nucleotide polymorphisms (SNPs) related to the vascular endothelial growth factor (VEGF) gene. Methods: The patients who were diagnosed with AMD were included in this prospective study. Three SNPs (rs1413711, rs2146323, and rs3025033) of the VEGF gene were genotyped by real-time polymerase chain reaction in the genomic DNA isolated from peripheral blood samples of the 82 patients and 80 controls. Results: The genotype frequencies of rs1413711 and rs2146323 were not significantly different between the study group and the control group (P=0.072 and P=0.058). However, there was a significant difference in the genotype frequencies of these SNPs between the wet type AMD and dry type AMD (P=0.005 and P=0.010, respectively). One of the SNPs (rs1413711) was also found to be associated with the severity of AMD (P=0.001) with significant genotype distribution between early, intermediate, and advanced stages of the disease. The ancestral alleles were protective for both SNPs while the polymorphic alleles increased the risk for dry AMD. Conclusion: VEGF SNPs rs1413711 and rs2146323 polymorphisms are significantly associated with AMD subtypes in our population.
    International Journal of Ophthalmology 10/2014; 7(5):773-7. DOI:10.3980/j.issn.2222-3959.2014.06 · 0.12 Impact Factor
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    ABSTRACT: A 30-year-old male patient referred to our clinic for unraveling the underlying etiology of the azoospermia. He had no unusual medical history. At physical examination, obesity, short neck and gynecomastia were noted. All hormone levels were normal except estradiol which was 2-fold higher than the upper limit. Having azoospermia in the spermiogram, scrotal ultrasonography was normal. Cytogenetic analysis and fluorescence in situ hybridization were performed subsequently, 45,X,add(21)(p10) and 45,X,add(21)(p10).ish der(Y;21) (q12;p10) were found, respectively. On C-banding, dicentric staining of translocated chromosome was observed. NOR banding was negative. Molecular genetics studies using multiplex polymerase chain reaction revealed the presence of Y chromosome sequences at SRY, AZFa, AZFb, AZFc regions.
    Turkiye Klinikleri Journal of Medical Sciences 12/2012; 32(6):1732-1736. DOI:10.5336/medsci.2011-23453 · 0.10 Impact Factor
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    ABSTRACT: DNA repair plays a key role in prevention of carcinogenesis and one of the most important DNA repair mechanisms is nucleotide excision repair (NER) pathway. This pathway includes a number of genes such as excision repair cross-complementing group 1 (ERCC1) gene which are responsible for the 5' incision of damaged DNA. A reduced DNA repair capacity associated with ERCC1 mRNA level has been observed in lung carcinogenesis. Two single nucleotide polymorphisms (SNPs) in ERCC1 gene, T19007C (rs11615) and C8092A (rs3212986), reportedly predict to affect the mRNA of ERCC1 in non-small cell lung cancer (NSCLC). To examine the role of two common SNPs in ERCC1 gene further, we conducted this study where 80 cases histopatologically diagnosed as NSCLC were genotyped. Genomic DNA was extracted from formalin-fixed, paraffin embedded tissues and two SNPs were analyzed using real-time PCR. The distributions of TT, TC, and CC genotypes of the T19007C SNP were 40, 44 and 16%, respectively. Significantly increased frequency of the patients carrying at least one 19007C allele was observed in early stage compared to advanced stage (P=0.002). And also, the frequency of TC and CC genotypes significantly increased in younger patients compared to older patients (P=0.035). Regarding C8092A SNP, the distribution of CC, CA, and AA genotypes was 38, 51 and 11%, respectively. There was no significant difference in the genotype distribution between C8092A SNP and clinicopathological parameters. This study indicated that harboring at least one 19007C allele may have protective effect in NSCLC.
    Molecular Biology Reports 05/2011; 39(1):375-80. DOI:10.1007/s11033-011-0748-8 · 2.02 Impact Factor
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    ABSTRACT: Excision Repair Cross-Complementing Group 1 (ERCC1) is an important DNA repair gene, playing critical role in nucleotide excision repair pathway and having a significant influence on genomic instability. Some studies support that ERCC1 might be a potential predictive and prognostic marker in non-small cell lung cancer (NSCLC). ERCC1 has also been shown to be a promising biomarker in NSCLC treated with a cisplatin-based regimen. Therefore, the determination of ERCC1 expression at DNA, mRNA and protein level in different stages of NSCLC is still an important topic in the cancer. Ninety-one formalin-fixed paraffin-embedded tumor samples histopathologically diagnosed as NSCLC were examined in this study. ERCC1 expression at protein level were scored by immunohistochemistry. The gene amplification and mRNA expression levels for ERCC1 were determined by real-time quantitative PCR. There was complete concordance among the three methods in 39 tumor samples (42.9%). A strong correlation was found between DNA amplification and mRNA expression (r=0.662) while there was no correlation between mRNA and protein assessment for ERCC1 expression (r=-0.013). ERCC1 expression at mRNA and DNA level (63.1 and 84.2%, respectively) in tumors at stage III was higher than at the other stages. In contrast, the protein expression at stage II and III (56.6 and 52.6%, respectively) of NSCLC was lower than that of tumors with stage I NSCLC. These results show that the mechanism by which ERCC1 expression might play a role in tumor behavior. This study was also confirmed that the appropriate validation and qualification in methods used for ERCC1 status were needed before its clinical application and implementation.
    Molecular Biology Reports 05/2011; 39(1):335-41. DOI:10.1007/s11033-011-0743-0 · 2.02 Impact Factor
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    ABSTRACT: The current study was undertaken to investigate chromosomal and genetical aberrations leading to overexpression of Topoisomerase-2α (TOP2α) and to reveal the possible association of these aberrations with HER2/neu overexpression and gene amplification, and to search for the relationship between TOP2α and HER2/neu status with prognostical biomarkers in papillary renal cell carcinoma (RCC), a group of tumors with diverse molecular, chromosomal and clinical features. Archival cases of papillary RCC obtained from Departments of Pathology of Pamukkale, Ege and Dokuz Eylul Universities were studied in two groups (type 1 and type 2) each containing 20 cases. The level of TOP2α and HER2/neu expression by tumor cells were determined immunohistochemically. A multicolor FISH probe was used to define both amplification of HER2/neu and TOP2α genes, and polysomy 17. The ratio of cells expressing TOP2α in type 1 and type 2 papillary RCC were 24.29% and 6.89%, respectively. The difference was statistically significant comparing the average or median values of groups separately (p = 0.002). The expression levels of TOP2α and HER2/neu were also correlated. TOP2α and HER2/neu were co-amplified in both groups. Immunohistochemical expression was not observed in 15 of 23 cases with HER2/neu amplification. The most frequent finding detected by FISH method was polysomy of chromosome 17. We had contradictory results compared with the findings reported in the limited numbers of literature. It shows us that papillary RCC constitute a heterogenous group of tumors with various cytogenetic features and morphological classification of these tumors may not be compatible with their molecular characteristics.
    Pathology & Oncology Research 04/2011; 17(3):697-703. DOI:10.1007/s12253-011-9372-0 · 1.86 Impact Factor
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    ABSTRACT: Neonatal thrombosis is a serious event that can cause mortality or severe morbidity. Although catheters are the most common cause of neonatal thrombosis, spontaneous events can also occur. Arterial thrombosis is very rare and accounts for approximately half of all thrombotic events in neonates. Genetic prothrombotic risk factors may affect the occurence of neonatal thrombosis. In this report, a case of left brachial, radial, and ulnar arterial thrombosis associated with methylene-tetrahydrofolate reductase (MTHFR) gene C677T and A1298C polymorphism heterozygosity is presented. Plasma homocysteine level and other prothrombotic components were normal. Standard heparin, aspirin, vitamin 1312, 86 and folic acid were initiated for treatment. However, the left arm of the patient was amputated at the shoulder because its capillary stream could not be observed. We suggest that MTHFR gene C677T and A1298C polymorphism heterozygosity might be investigated in neonates with congenital arterial thrombosis in spite of normal serum homocysteine levels.
    Medical Journal of Trakya University / Trakya Universitesi Tip Fakultesi Dergisi 01/2009; 28(3). DOI:10.5174/tutfd.2009.03229.2 · 0.11 Impact Factor
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    ABSTRACT: A large number of studies have shown that the prevalence of somatic chromosome abnormalities detectable with karyotyping is higher in infertile men. However, a normal somatic karyotype does not exclude the chance of having low level mosaicism. Eleven men with severe oligozoospermia and 10 healthy, fertile men were included in this study. All the patients had severe oligozoospermia with sperm counts < or =3,000,000/ mL. All participants had normal physical findings and testicular volume. The probe for dual-color fluorescence in situ hybridization consisted of an alpha satellite sequence in the centromeric region of chromosome X (DXZ1) and satellite III DNA at the Yq12 region of chromosome Y (DYZ1). The sex chromosome aneuploidy rate was significantly higher in subjects than in controls (p<0.001). The median incidence of sex chromosome aneuploidy in the oligozoospermic group was 4.5% (range, 0.8-7.3%), while in the control group it was 0.7% (range, 0.2-1.2%)., The incidence of aneuploidy in somatic cells is significantly greater in oligozoospermic men than in normal controls. That may suggest that chromosome instability is a result of altered genetic control during mitotic cell division. Our results demonstrate that men with oligozoospermia have an elevated risk for sex chromosome abnormalities in their somatic cells.
    The Journal of reproductive medicine 06/2006; 51(6):489-92. · 0.70 Impact Factor
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    ABSTRACT: This population-based study on parkinsonism in a genetically isolated community from a rural area of Turkey aimed to provide a selective evaluation of environmental and heritable risk factors. An increased prevalence of parkinsonism (4.1%) was detected in the village of Kizilcaboluk for people 65 years of age and older. This study included 36 patients with parkinsonism living in Kizilcaboluk and three times that number of age- and sex-matched people serving as controls. A questionnaire including demographic data, family history, education, occupation, data on exposures to pesticides, smoking, alcohol intake, and head trauma was administered. We found a significant association of parkinsonism cases with a positive family history in first-degree relatives (odds ratio [OR], 7.48; 95% confidence interval [CI], 2.52-22.17; P < 0.0001) and with pesticide exposure (OR, 2.96; 95% CI, 1.31-6.69; P = 0.015) compared to the control subjects. The value of genetically isolated populations for the identification of genetic risk factors for common and complex disorders has gained much attention recently because the genetic make-up of these populations is likely to be less complex than that of the general population and our findings should prompt investigations to the nature of a familial aggregation of parkinsonism in this population.
    Movement Disorders 07/2003; 18(7):799-804. DOI:10.1002/mds.10440 · 5.68 Impact Factor
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    ABSTRACT: Cytogenetic studies in patients with reproductive failure To investigate the contribution of chromosomal abnormalities in sub fertility and in couples with repeated abortions. Hundred and 13 couples who had at least two or more spontaneous abortions and 65 women and 63 men with infertility were analyzed cytogenetically. Major chromosomal rearrangements were found in 8% and minor variants in 6% in the study population. Major chromosomal aberrations were judged to explain 4.9% of recurrent abortions and 13% of infertility. Chromosomal abnormalities in infertile men occurred in 5% and in infertile women in 21.5%. The chromosomal abnormalities were structural (57%), numerical (18%) or mosaics (25%). Chromosomal aberrations in recurrent abortions are mostly structural ones and those in female infertility mosaicism of sex chromosomes. Turner's syndrome, Turner variants and XY females are detected as a cause of female infertility. The structural and numerical aberrations of either sex or autosomal chromosomes were found in infertile men.
    Acta Obstetricia Et Gynecologica Scandinavica 02/2003; 82(1):53-6. DOI:10.1034/j.1600-0412.2003.820109.x · 2.43 Impact Factor