Yazıcı, Hülya
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Yazici, Hulya; Yazici, H.; Yazici, H; Yazici, Hulya Julie
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10.03. Temel Tıp Bilimleri Bölümü
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7
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8
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9
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22
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74
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847
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17
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72
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736
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24
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23
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6/642
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202
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65
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4
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4
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WoS Citations per Publication
8.42
Scopus Citations per Publication
2.71
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16
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0
| Journal | Count |
|---|---|
| Sabiad | 4 |
| Turk Onkoloji Dergisi-Turkish Journal of Oncology | 3 |
| Pathology Research and Practice | 3 |
| Biochemical Genetics | 3 |
| Cancer Medicine | 2 |
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Now showing 1 - 10 of 24
Article Citation - WoS: 12Citation - Scopus: 13Breast Cancer in East Africa: Prevalence and Spectrum of Germline SNV/Indel and CNVs in BRCA1 and BRCA2 Genes among Breast Cancer Patients in Tanzania(Wiley, 2023) Rweyemamu, Linus P.; Gultaslar, Busra K.; Akan, Gokce; Dharsee, Nazima; Namkinga, Lucy A.; Lyantagaye, Sylvester L.; Atalar, FatmahanBackground Growing prevalence and aggressiveness of breast cancer (BC) among East African women strongly indicate that the genetic risk factor implicated in the etiology of the disease may have a key role. Germline pathogenic variants in BRCA1 and BRCA2 (BRCA1/2) are known to increase the lifetime risk of BC. This study investigated the prevalence and spectrum of germline single nucleotide variant/insertion and deletion (SNV/indel), and copy number variations (CNVs) in BRCA1/2 among Tanzanian BC patients, and evaluated the associations of identified variants with patient's socio-demographic and histopathological characteristics. Methods One hundred BC patients were examined for BRCA1/2 variants using next-generation sequencing (NGS). Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA) assay were performed for the confirmation of SNV/indel and CNVs, respectively. Results Six germline SNV/indel pathogenic variants were detected from six unrelated patients. Five of these variants were identified in BRCA1, and one in BRCA2. We also identified, in one patient, one variant of uncertain clinical significance (VUS). CNV was not detected in any of the BC patients. Furthermore, we found that in our cohort, BRCA1/2 variant carriers were triple-negative BC patients (p = 0.019). Conclusions Our study provides first insight into BC genetic landscape by the use of NGS in the under-represented East African Tanzanian populations. Our findings support the importance of genetic risk factors in BC etiology in Tanzania and showed a relatively high overall prevalence (6%) of germline BRCA1/2 pathogenic variants in BC patients. Therefore, our results indicate that BRCA1/2 pathogenic variants may well contribute to BC incidence in Tanzania. Thus, the identification of frequent variants in BRCA1/2 genes will enable implementation of rapid, inexpensive population-specific BRCA1/2 genetic testing, particularly for triple-negative BC patients known for their high prevalence in Tanzania. This will, in turn, greatly contributes to provide effective therapeutic strategies.Article Citation - WoS: 2Citation - Scopus: 3Aberrant miR-3135b and miR-1273g-3p Expression in the Peripheral Blood Samples of BRCA1/2 (±) Ovarian Cancer Patients(Elsevier Ltd, 2024) Tuncer, Seref Bugra); Celik, Betul; Erciyas, Seda Kilic; Erdogan, Ozge Sukruoglu; Pasin, Ozge; Avsar, Mukaddes; Gultaslar, Busra Kurt; Ghafour, Arash Adamnejad; Uyaroglu, Gamze; Odemis, Demet Akdeniz; Yazici, HulyaOvarian cancer (OC) ranks as the eighth most prevalent malignancy among women globally. The short non-coding RNA molecules, microRNAs (miRNAs) target multiple mRNAs and regulate the gene expression. Here in this study, we aimed to validate miR-3135b and miR-1273g-3p as novel biomarkers for prognostic and diagnostic factor OC. After RNA isolation, we analyzed the miR-3135b and miR-1273g-3p expression in peripheral blood samples derived from 150 OC patients. Subsequently, we compared their expression levels with 100 healthy controls. The differences of miR-3135b and miR-1273g-3p expression were detected using the Quantitative Real Time-PCR (qRT-PCR) technique following miRNA-specific cDNA synthesis pursing miRNA separation. The miR-3135b and miR-1273g-3p were higher in OC patients who tested positive for BRCA1/2 compared to BRCA-negative patients, and healthy cases. The level of miR-3135b demonstrated a roughly 4.82-fold increase in OC patients in comparison to the healthy cases, while miR-1273g-3p expression exhibited a roughly 6.77-fold increase. The receiver operating characteristic (ROC) analysis has demonstrated the potential of miR-3135b and miR-1273g-3p as markers for distinguishing between OC patients and healthy controls. The higher expressions of miR-3135b and miR-1273g-3p could be associated with OC development. Moreover, miR-3135b may have a diagnostic potential and miR-1273g-3p may have both diagnostic and prognostic potential in OC cell differentiation. The string analysis has revealed an association between miR-1273g-3p and the MDM2 gene, suggesting a potential link to tumor formation through the proteasomal degradation of the TP53 tumor suppressor gene. Additionally, the analysis indicates an association of miR-1273g-3p with CHEK1, a gene involved in checkpoint-mediated cell cycle arrest. String analysis also indicates that miR-3135b is associated with the MAPK1 gene, causing activation of the oncogenesis cascade. In conclusion, miR-1273g-3p, and miR-3135b exhibit significant potential as diagnostic markers. However, further research is needed to comprehensively investigate these miRNAs diagnostic and predictive characteristics in a larger cohort. © 2023 The AuthorsReview Thyroid Hormone Resistance with Succinate Dehydrogenase-B Gene Mutation(Edizioni Minerva Medica, 2022) Erel, Cansu; Cakmak, Ramazan; Ullari, Hulya Hacisahinog; Artan, Selay; Ayse, Kubat Uzum; Aral, Ferihan; TANAKOl, Refik; Yazici, HulyaResistance to thyroid hormone (RTH) is characterized by non-suppressed TSH concentration despite high T4 and/or T3 levels.1 Resistance may develop at any steps in the hormone receptor binding, signaling, or intracellular thyroid hormone metabolism process. The disease is caused by mutations in the thyroid hormone receptor beta (THRB) in the majority of cases.2 Mutations in other genes have been associated with RTH, including thyroid hormone receptor alpha (THRA), Monocarboxylate transporter-8 (MCT8), and selenocysteine insertion sequence binding protein 2 (SECISBP2).2, 3 After clinical and laboratory examinations, genetic screening of other family members is necessary in suspicious cases. Succinate dehydrogenase subunit B (SDHB) is a well-known gene related to pheochromocytoma and extra-adrenal paragangliomas in the head and neck.4-6 The patient as well as his two children who have been diagnosed with RTH, all are found to have SDHB mutations that are functionally significant. This is the first report an SDHB mutation has been recorded in an RTH case in the medical literature. A 50-yearold man evaluated preoperatively for nasal surgery showed hyperthyroidism, and he was prescribed methimazole orally. An ultrasound of his enlarged thyroid gland revealed a 13 mm haloed cystic necrotic nodule. The nodule was diagnosed as Bethesda IV suspicious for follicular neoplasia after a fine-needle aspiration biopsy. His laboratory findings were FT3:13.7 pmol/L (3.1-6.8), FT4: 20.5 pmol/L (12-22), and TSH:1.0 mIU/mL (0.27-4.2). He was planned for a total thyroidectomy in the euthyroid state and referred to our department. He had mild hyperthyroid symptoms, including excessive sweating and agitation. He was shorter than the population’s average height. He had a goiter and tachycardia on his physical examination. On repeated testing, his laboratory findings revealed a high FT3 level. Antibody interaction misleading results in polyethyleneglycol precipitated thyroid hormones were investigated, and comparable results were found. Scintigram and negative thyroid auto-antibodies ruled out Graves’ disease. Normal anterior pituitary hormone levels and a hypophysial MRI ruled out a pituitary adenoma. Drug-induced hyperthyroidism and acute non-thyroidal disease were not taken into consideration. His brother, his son, and his daughter had incompatible thyroid hormone concentrations as the index case (Table I).Article Citation - WoS: 4Citation - Scopus: 4miRNA Sequence Analysis in Patients with Kaposi's Sarcoma-Associated Herpesvirus(Frontiers Media SA, 2022) Tunçer, Şeref Buğra; Çelik, Betül; Akdeniz Ödemiş, Demet; Kılıç Erciyas, Seda; Şükrüoğlu Erdoğan, Özge; Avşar, Mukaddes; Kuru Türkcan, Gözde; Yazıcı, Hülya; Tuncer, Seref Bugra; Celik, Betul; Akdeniz Odemis, Demet; Kilic Erciyas, Seda; Sukruoglu Erdogan, Ozge; Avsar, Mukaddes; Yazici, HulyaMicroRNAs (miRNAs) are the non-coding RNAs that can both attach to the untranslated and coding sections of target mRNAs, triggering destruction or post-transcriptional alteration. miRNAs regulate various cellular processes such as immune function, apoptosis, and tumorigenesis. About 35,000 miRNAs have been discovered in the human genome. The increasing evidence suggests that the dysregulation of human miRNAs may have a role in the etiology of some disorders including cancer. Only a small sub-set of human miRNAs has functionally been validated in the pathogenesis of oncogenic viruses such as Kaposi's sarcoma-associated herpesvirus (KSHV). KSHV is the cause of various human malignancies including primary effusion lymphoma (PEL) and Kaposi's sarcoma (KS), which are mainly seen in AIDS patients or other immunocompromised people. We aimed to identify the miRNAs in Kaposi's sarcoma cases, with the comparison of KSHV seropositive and seronegative tumors with the controls and in each other in Turkish Kaposi's sarcoma patients. We performed the miRNA-sequencing at genome level in the peripheral blood mononuclear cells of 16 Kaposi's sarcoma patients, and in 8 healthy controls matched for age, gender, and ethnicity. A total of 642 miRNA molecules with different expression profiles were identified between the patients and the healthy controls. Currently, out of 642 miRNAs, 7 miRNAs (miR-92b-3p, miR-490-3p, miR-615-3p, miR-629-5p, miR-1908, miR-3180, miR-4433b-3p) which have not been described in the literature in the context of Kaposi's sarcoma were addressed in the study for the first time and 9 novel miRNAs, not found previously in the database, have been detected in Kaposi's sarcoma using the miRNA-sequencing technique. This study demonstrates the identification of differently expressed miRNAs which might be the new therapeutic targets for Kaposi's sarcoma, that has limited treatment options and can be used in the etiology, diagnosis, and prognosis of this cancer.Article Citation - WoS: 152Tuberous Sclerosis Complex and Cancer(Istanbul Tip Fakultesi, 2023) Doğan, T.; Yazici, H.Tuberous sclerosis complex (TSC) is a neurocutaneous syndrome that can affect multiple organ systems such as the brain, heart, and lung, and neurological disorders such as autism spectrum disorder and mental retardation can be observed along with epileptic seizures in affected individuals. The disease can occur at any age. A genetic disease of TSC develops due to the mutations in TSC1 and TSC2 genes that cause dysfunction in Tuberin and/or Hamartin proteins. Although the disease has a highly variable penetrance, the cellular signal transduction mechanisms of TSC-related genes have largely been elucidated. The diagnostic criteria created by International TSC Consensus Group in 2012 are used in the diagnosis of the syndrome in addition to the genetic tests. At present, it is estimated that there are approximately 2 million people with TSC worldwide and 50,000 people are affected by the disease in the USA alone. It is important to know about the molecular genetics and clinical features of the disease for targeted therapies and well-managed surveillance. In the present study, we aimed to examine the genetic, biological, and clinical features of TSC and to discuss the genetic counseling approach that should be applied to patients with TSC. © 2023, Turkish Society for Radiation Oncology.Article Citation - WoS: 1Citation - Scopus: 1High Expression of miR-218-5p in the Peripheral Blood Stream and Tumor Tissues of Pediatric Patients with Sarcomas(Springer, 2024) Ozdenoglu, Fazilet Yildiz; Odemis, Demet Akdeniz; Erciyas, Seda Kilic; Tuncer, Seref Bugra; Gultaslar, Busra Kurt; Salduz, Ahmet; Buyukkapu, Sema; Olgac, Necat Vakur; Kebudi, Rejin; Yazici, HulyaSarcomas are malignant tumors that may metastasize and the course of the disease is highly aggressive in children and young adults. Because of the rare incidence of sarcomas and the heterogeneity of tumors, there is a need for non-invasive diagnostic and prognostic biomarkers in sarcomas. The aim of the study was to investigate the level of miR-218-5p in peripheral blood and tumor tissue samples of Ewing's sarcoma, osteosarcoma, spindle cell sarcoma patients, and healthy controls, and assessed whether the corresponding molecule was a diagnostic and prognostic biomarker. The study was performed patients (n = 22) diagnosed and treated with Ewing's sarcoma and osteosarcoma and in a control group of 22 healthy children who were matched for age, gender, and ethnicity with the patient group. The expression level of miR-218-5p in RNA samples from peripheral blood and tissue samples were analyzed using the RT-PCR and the expression level of miR-218-5p was evaluated by comparison with the levels in patients and healthy controls. The expression level of miR-218-5p was found to be statistically higher (3.33-fold, p = 0.006) in pediatric patients with sarcomas and when the target genes of miR-218-5p were investigated using the bioinformatics tools, the miR-218-5p was found as an important miRNA in cancer. In this study, the miR-218-5p was shown for the first time to have been highly expressed in the peripheral blood and tumor tissue of sarcoma patients. The results suggest that miR-218-5p can be used as a diagnostic and prognostic biomarker in sarcomas and will be evaluated as an important therapeutic target.Article Citation - WoS: 1Citation - Scopus: 1Germline Mutational Variants of Turkish Ovarian Cancer Patients Suspected of Hereditary Breast and Ovarian Cancer (HBOC) by Next-Generation Sequencing(Elsevier GmbH, 2024) Tuncer, Seref Bugra; Celik, Betul; Erciyas, Seda Kilic; Erdogan, Ozge Sukruoglu; Gultaslar, Busra Kurt; Odemis, Demet Akdeniz; Avsar, Mukaddes; Sen, Fatma; Saip, Pinar Mualla; Yazici, HulyaHereditary Breast and Ovarian Cancer (HBOC) syndrome is characterized by an increased risk of developing breast cancer (BC) and ovarian cancer (OC) due to inherited genetic mutations. Understanding the genetic variants associated with HBOC is crucial for identifying individuals at high risk and implementing appropriate preventive measures. The study included 630 Turkish OC patients with confirmed diagnostic criteria of The National Comprehensive Cancer Network (NCCN) concerning HBOC. Genomic DNA was extracted from peripheral blood samples, and targeted Next-generation sequencing (NGS) was performed. Bioinformatics analysis and variant interpretation were conducted to identify pathogenic variants (PVs). Our analysis revealed a spectrum of germline pathogenic variants associated with HBOC in Turkish OC patients. Notably, several pathogenic variants in BRCA1, BRCA2, and other DNA repair genes were identified. Specifically, we observed germline PVs in 130 individuals, accounting for 20.63% of the total cohort. 76 distinct PVs in genes, BRCA1 (40 PVs), BRCA2 (29 PVs), ATM (1 PV), CHEK2 (2 PVs), ERCC2 (1 PV), MUTYH (1 PV), RAD51C (1 PV), and TP53 (1PV) and also, two different PVs (i.e., c.135–2 A>G p.? in BRCA1 and c.6466_6469delTCTC in BRCA2) were detected in a 34-year-old OC patient. In conclusion, our study contributes to a better understanding of the genetic variants underlying HBOC in Turkish OC patients. These findings provide valuable insights into the genetic architecture of HBOC in the Turkish population and shed light on the potential contribution of specific germline PVs to the increased risk of OC. © 2024 Elsevier GmbHArticle Observation of a Structure in E+e- → Φη′ at √s from 2.05 to 3.08 GeV(2023) Yazıcı, Hülya; Tuncer, Seref Bugra; Kebudi, Rejin; Bay, Sema Büyükkapu; Odemis, Demet Akdeniz; Erdogan, Ozge Sukruoglu; Çelik, BetülAmaç: Sarkomlar, yağ, kas, kan damarları, sinir, derin cilt dokuları ile fibröz dokular dahil olmak üzere kemiklerde ve yumuşak dokularda gelişen nadir kanserlerdir. Kişinin sarkom geliştirme riskini artırabilecek genetik yatkın lık, radyoterapi öyküsü ve kimyasal maruziyet gibi bazı faktörler olmasına rağmen, çoğu sarkomun bilinen bir nedeni yoktur ve günümüzde genetik temeli tam olarak aydınlatılmamıştır. Gereç ve Yöntem: Ailesinde çeşitli sarkom tanıları bulunan yüksek risk taşıdığı düşünülen 2 farklı aileden seçilmiş hastalarda hastalığın hangi gen ya da genler aracılığı ile geliştiğini belirlemek amacıyla tüm ekzom dizile me (WES) işlemi yapılmıştır. Bulgular: Çalışma sonunda ilk ailede patojenik kaydı bulunan toplam 17 varyant tanımlanırken bu varyantlardan KLKB1, IRGM, PRSS1, MBL2, PTPRJ, FGFR4 ve SLC34A3 olmak üzere 7 farklı gene ait toplam 8 patojenik varyant çeşitli kanser riskleri ile ilişkilendirilmiştir. İkinci ailede ise FGFR4, MBL2, MUTYH, NQO1 olmak üzere 4 farklı gene ait 4 patojenik varyant tanımlanmıştır. Sonuç: Sarkom açısından yüksek risk taşıyan kişilerin incelenmesi ve has talık ile ilişkili olabilecek genlerin bulunması ile gerek hastaların gerekse riskli aile bireylerinin takip protokolüne önemli katkılar sağlanmıştır. Ayrıca çıkan sonuçlar doğrultusunda ailelerde yapılmış risk analizi sonrası kanser yatkınlığı olan aile bireyleri seçilmiş ve erken tanı avantajı sağlanabilmesi için gerekli tetkik ve taramalar önerilmiştir.Article Citation - Scopus: 3Genetic Alterations in Lung Cancer(Kare Publ, 2024) Bayramova, Jamila; Tarakci, Elif; Huseynova, Gumru; Yazici, Hilal; Yazici, HulyaLung cancer is the leading cause of cancer -related deaths worldwide. Due to the prevalence of late -stage diagnoses, treatment options are frequently constrained. Molecular profiling of lung cancer is crucial for the clinical management and successful therapy of the disease because lung cancer originates from a multilayered carcinogenesis consisting of multiple genetic and epigenetic abnormalities. The potential of anomalies involved in carcinogenesis as biomarkers that can be used in the diagnosis and treatment of lung cancer has begun to be evaluated due to the development of new generation sequencing methods and their more frequent application in the clinic. This review presents information regarding the genetic alterations responsible for the malignant transformation of lung cells. The article highlights the predominant gene mutations that are specific to a particular subtype of lung cancer, their impact on the clinical progression of the disease, and the response to treatment. However, in summarizing all genetic features, the latest information from the NCCN v2.2024 guide was taken into account.Article Citation - WoS: 9Citation - Scopus: 8Evaluation of BRCA1/2 Gene Mutations in Patients with High-Risk Breast and/or Ovarian Cancer in Turkey(Walter de Gruyter GmbH, 2022) Akdeniz Ödemiş, Demet; Çelik, Betül; Kılıç Erciyas, Seda; Şükrüoğlu Erdoğan, Özge; Tuncer, Şeref Buğra; Kurt Gültaşlar, Büşra; Adamnejad Ghafour, Arash; Saip, Pınar; Yazıcı, Hülya; Akdeniz Odemis, Demet; Celik, Betul; Kilic Erciyas, Seda; Sukruoglu Erdogan, Ozge; Tuncer, Seref Bugra; Kurt Gultaslar, Busra; Yazici, HulyaObjectives To find BRCA1/2 test selection criteria unique to the Turkish population, as well as to provide the BRCA1/2 gene mutation distributions of patient population to the literature. Methods Genetic counseling was given to 2,373 cases with a family history of high-risk breast and/or ovarian cancer who applied to Istanbul University, Oncology Institute, Department of Cancer Genetics between 1994 and 2021 and selected by NCCN Guidelines for the BRCA1/2 test criteria. In our clinic, mutation screenings in BRCA1/2 genes were performed by Sanger sequencing method in patients admitted between 1994 and 2014 and by NGS method in patients admitted between 2015 and 2021. Results The overall mutation rate in our patient group selected from high-risk patients was 16.5% (391/2,373) after BRCA1/2 gene mutation screening performed in 2,373 cases who applied to the Cancer Genetics clinic. Of the patients with mutations, 57.5% (225/391) had BRCA1 mutation, 41.9% (164/391) had BRCA2 mutation, and 0.6% (2/391) had both BRCA1 and BRCA2 pathogenic mutations. People diagnosed before the age of 60 who have a history of triple-negative breast cancer had a 28.5% overall mutation rate. Conclusions BRCA1/2 mutation in Turkish population were evaluated in accordance with NCCN BRCA1/2 genetic test selection criteria; we discovered that all of our study results were statistically significant (p<0.05).
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