Browsing by Author "Islekel, Gul Huray"

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Citation - WoS: 1
Citation - Scopus: 1
Development and Validation of an Lc-ms/Ms Method for D- and L-2 Acid Measurement in Cerebrospinal Fluid, Urine and Plasma: Application To Glioma
(Future Sci Ltd, 2022) Dal-Bekar, Nazli Ecem; Tuna, Gamze; Islekel, Sertac; Islekel, Gul Huray
Aim: IDH mutations have been identified as frequent molecular lesions in several tumor types, particularly in gliomas. As a putative marker of IDH mutations, elevated D-2-HG has been reported in glioma, acute myeloid leukemia and intrahepatic cholangiocarcinoma. Excessive production of L-2-HG has also been described in renal cell carcinoma and 2-hydroxyaciduria. Materials & methods: The authors present a fully optimized stable isotope dilution multiple reaction monitoring method for quantification of D-/L-2-HG using LC-MS/MS. This is the first method validation study performed on cerebrospinal fluid, plasma and urine demonstrating clinical applicability with samples from glioma patients. Results & conclusion: This method validation study showed high accuracy and precision with low limit of detection and limit of quantification values. The authors believe that the presented approach is highly applicable for basic and clinical research on related pathologies.
Citation - WoS: 10
Citation - Scopus: 11
Minimally Invasive Detection of Idh1 Mutation With Cell-Free Circulating Tumor Dna and D-2 D/L-2-hydroxyglutarate Ratio in Gliomas
(Oxford Univ Press Inc, 2022) Tuna, Gamze; Dal-Bekar, Nazli Ecem; Akay, Ali; Ruksen, Mete; Islekel, Sertac; Islekel, Gul Huray
Isocitrate dehydrogenase-1 (IDH1) mutation is accepted as one of the earliest events in tumorigenesis in gliomas. This mutation causes preferential accumulation of D- relative to L-enantiomer of 2-hydroxyglutarate (2-HG). Minimally invasive techniques to detect IDH1 mutation may prove useful for clinical practice. We adopted 2 different diagnostic approaches to detect IDH1 mutation status in glioma patients: Evaluation of D- and L-2-HG levels in cerebrospinal fluid (CSF), urine, and plasma, and identification of IDH1 mutation using cell-free circulating tumor DNA (ctDNA) in CSF and plasma. Forty-nine glioma patients in different stages were included. Levels of D- and L-2-HG were determined using liquid chromatography-tandem mass spectrometry; IDH1 R132H mutation was determined by digital-PCR. D-2-HG levels and D/L-2-HG ratio (rDL) in CSF and rDL in plasma were significantly higher in the mutant group than in the wild-type group (p = 0.029, 0.032, 0.001, respectively). The IDH1 mutation detection rates in CSF- and plasma-ctDNA were 63.2% and 25.0%, respectively. These data indicate that D-2-HG values in CSF and rDL in plasma and CSF can be considered as significant contributors to the identification of IDH1 mutation status. In addition, detection of IDH1 mutation in CSF-ctDNA from glioma patients provides a basis for future use of ctDNA for minimally invasive clinical assessment of gliomas.
Citation - WoS: 5
Citation - Scopus: 3
Urinary 8-Hydroxy Levels Are Elevated in Patients With Idh1-Wildtype Glioblastoma and Are Associated With Tumor Recurrence in Gliomas
(Elsevier, 2023) Tuna, Gamze; Bekar, Nazli Ecem Dal; Islekel, Sertac; Islekel, Gul Huray
2021 World Health Organization (WHO) Central Nervous System (CNS) Tumor Classification includes molecular diagnostic parameters such as isocitrate dehydrogenase (IDH) mutation or 1p19q codeletion status, in addition to the classical histological classification. Several studies have revealed that patients with IDH1 mutation have a longer survival rate compared to wildtype individuals. In glioma cells, increased oxidative stress has been identified. However, till now, the relation between oxidative stress levels and IDH1 mutation status in those patients was not examined. Therefore, the aim of this study was to investigate the urinary levels of oxidatively induced DNA damage products, 8-hydroxy-2 '- deoxyguanosine (8-OH-dG), (5 ' R) and (5 ' S)-8,5 '-cyclo-2 '-deoxy-adenosines (R-cdA and S-cdA) as reliable oxidative stress markers in patients with IDH1-wildtype (n = 20) and IDH1-mutant (n = 22) glioma. Absolute quantification of 8-OH-dG, R-cdA and S-cdA was achieved by liquid chromatography-tandem mass spectrometry with isotope dilution. The levels of 8-OH-dG were significantly greater in IDH1-wildtype glioma patients than those in IDH1-mutant ones (p = 0.017). No statistically significant difference was observed for R-cdA and S-cdA levels. 8-OH-dG levels were positively correlated with patients' tumor recurrence in all patients (r = 0.382, p = 0.014). The mutation status of glioma is well correlated with oxidative stress. Examination of noninvasively measured oxidative DNA damage products along with IDH1 mutation status in glioma patients, might be particularly important in terms of evaluating and monitoring the effectiveness of treatment.