Browsing by Author "Tunca, Berrin Türkei"
Now showing 1 - 8 of 8
- Results Per Page
- Sort Options
Item Evaluation of genetic variations in miRNA-binding sites of BRCA1 and BRCA2 genes as risk factors for the development of early-onset and/or familial breast cancer(Asian Pacific Organization Cancer Prevention, 2014) Ertürk, Elif; Çeçener, Gülşah; Polatkan, Volkan; Gökgöz, Şehsuvar; Egeli, Ünal; Tunca, Berrin Türkei; Tezcan, Gülçin; Demirdöğen, Elif; Ak, Seçil; Taşdelen, İsmet; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Genel Cerrahi Anabilim Dalı.; 0000-0002-1619-6680; 0000-0001-7904-883X; 0000-0002-3820-424X; 0000-0002-5956-8755; ABI-6078-2020; F-8554-2017; AAK-3371-2021; AAH-1420-2021; AAH-3843-2020; AAP-9988-2020; 50261655300; 6508156530; 56399309200; 6603238737; 55665145000; 6602965754; 25650627600; 25644460900; 55253485700; 9637821500Although genetic markers identifying women at an increased risk of developing breast cancer exist, the majority of inherited risk factors remain elusive. Mutations in the BRCA1/BRCA2 gene confer a substantial increase in breast cancer risk, yet routine clinical genetic screening is limited to the coding regions and intronexon boundaries, precluding the identification of mutations in noncoding and untranslated regions. Because 3' untranslated region (3' UTR) polymorphisms disrupting microRNA (miRNA) binding can be functional and can act as genetic markers of cancer risk, we aimed to determine genetic variation in the 3' UTR of BRCA1/BRCA2 in familial and early-onset breast cancer patients with and without mutations in the coding regions of BRCA1/BRCA2 and to identify specific 3' UTR variants that may be risk factors for cancer development. The 3' UTRs of the BRCA1 and BRCA2 genes were screened by heteroduplex analysis and DNA sequencing in 100 patients from 46 BRCA1/2 families, 54 non-BRCA1/2 families, and 47 geographically matched controls. Two polymorphisms were identified. SNPs c.* 1287C>T (rs12516) (BRCA1) and c.* 105A>C (rs15869) (BRCA2) were identified in 27% and 24% of patients, respectively. These 2 variants were also identified in controls with no family history of cancer (23.4% and 23.4%, respectively). In comparison to variations in the 3' UTR region of the BRCA1/2 genes and the BRCA1/2 mutational status in patients, there was a statistically significant relationship between the BRCA1 gene polymorphism c.* 1287C>T (rs12516) and BRCA1 mutations (p=0.035) by Fisher's Exact Test. SNP c.* 1287C>T (rs12516) of the BRCA1 gene may have potential use as a genetic marker of an increased risk of developing breast cancer and likely represents a non-coding sequence variation in BRCA1 that impacts BRCA1 function and leads to increased early-onset and/or familial breast cancer risk in the Turkish population.Item FHIT gene sequence variants and reduced fhit protein expression in glioblastoma multiforme(Springer/Plenum Publishers, 2010-03) Güler, Gülnür; Aksoy, Kaya; Çeçener, Gülşah; Tunca, Berrin Türkei; Egeli, Ünal; Bekar, Ahmet; Tolunay, Şahsine; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Beyin ve Sinir Cerrahisi Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Patoloji Anabilim Dalı.; 0000-0002-3820-424X; 0000-0002-1619-6680; 0000-0001-7904-883X; AAP-9988-2020; AAI-1612-2021; ABI-6078-2020; AAH-1420-2021; 6508156530; 6602965754; 55665145000; 6603677218; 6602604390Molecular studies have an important role in the elucidation of the mechanisms involved in Glioblastoma multiforme (GBM) development. The occurrence of FHIT gene alterations, which has an important role in different cancers, has not yet been studied well in GBM. We aimed to investigate the occurrence of alterations of FHIT gene sequence and protein expression in the GBMs. Sequence alterations in exons 5-9 of the FHIT gene were screened in 63 GBMs using the single-strand conformational polymorphism method, followed by DNA sequencing. Additionally, the level of Fhit protein expression in tissues of 48 tumors was assessed by immunohistochemistry (IHC). In our investigation, FHIT gene alterations in the coding region were detected in 11 of the 63 GBM cases (17.5%). Two different sequence variants were determined: one novel missense variant (G -> C transition at codon 49) and one previously described silent alteration (C -> T transition at codon 88). Using web-based programs, such as SIFT and ESEfinder, it was determined that both alterations might have caused significant modification on protein function. In addition, we identified a previously reported an intronic polymorphism (T -> A transition at IVS8-17) in 47.5% of cases as a similar rate (45%) in the control group. Moreover, it was observed that Fhit protein expression was reduced in 87.5% of tumors. In conclusion, the reduction or loss of Fhit protein expression by genetic alterations or epigenetic mechanisms in GBM might be associated with brain tumorigenesis.Item Microsatellite instability status affects gene expression profiles in early onset colorectal cancer patients(Elsevier, 2013-12) Zorluoǧlu, Abdullah; Ak, Seçil; Tunca, Berrin Türkei; Yılmazlar, Tuncay; Tezcan, Gülçin; Çeçener, Gülşah; Egeli, Ünal; Öztürk, Ersin; Yerci, Ömer; Ertürk, Elif; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Bölümü.; Uludağ Üniversitesi/Tıp Fakültesi/Genel Cerrahi Bölümü.; Uludağ Üniversitesi/Tıp Fakültesi/Patoloji Bölümü.; 0000-0002-1619-6680; 0000-0001-7904-883X; 0000-0002-3820-424X; 0000-0002-5956-8755; ABI-6078-2020; AAH-3843-2020; AAH-1420-2021; F-8554-2017; AAP-9988-2020; AAK-3371-2021; 55253485700; 6602965754; 6701800362; 25650627600; 6508156530; 55665145000; 35070171400; 6603810549; 50261655300Background: The association between microsatellite instability (MSI) status and gene expression profiles in the early onset sporadic colorectal cancer (CRC) has not been clearly established. The aim of this study was to identify the altered gene expression patterns depending on the MSI status of early onset CRC and determine specific biomarkers that could provide novel therapeutic molecular targets in the Turkish population. Materials and methods: MSI markers (BAT25, BAT26, D2S123, D5S346, and D17S250) were investigated in tumors from 36 early onset sporadic CRC patients in whom gene expression profiles were analyzed previously. The relationship between the gene expression profiles depending on MSI status was evaluated. Results: A total of 15 tumors (16.66%) were identified as having MSI and 21 tumors (58.33%) were identified as having microsatellite stability (MSS). CK20 and MAP3K8 upregulation, observed in MSS tumors, was significantly associated with lymph node metastasis, recurrence, and/or distant metastasis and a short median survival (P < 0.05). REG1A upregulation is also correlated with recurrence and/or distant metastasis and a short median survival in patients with MSI tumors (P < 0.05). Conclusions: High expression levels of CK20 and MAP3K8 in MSS tumors and REG1A in MSI tumors correlated with a poor prognosis in CRC patients. Further studies and validations are required; these genes may provide novel therapeutic molecular targets for the development of anticancer drugs related to MSI status for early onset CRC treatment.Item Molecular markers for patients with thymic malignancies: Not feasible at present?(Asian Pacific Organization Cancer Prevention, 2014) Avcı, Nilüfer; Çeçener, Gülşah; Deligönül, Adem; Ertürk, Elif; Tunca, Berrin Türkei; Egeli, Ünal; Tezcan, Gülçin; Akyıldız, Elif Ülker; Bayram, Ahmet Sami; Gebitekin, Cengiz; Kurt, Ender; Evrensel, Türkkan; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Onkoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Patoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Göğüs Cerrahisi Anabilim Dalı.; Uludağ Üniversitesi/Sağlık Bilimleri Enstitüsü/Tıbbi Biyoloji Anabilim Dalı.; 0000-0002-1619-6680; 0000-0002-9732-5340; 0000-0003-0684-0900; 0000-0002-5956-8755; 0000-0002-3820-424X; 0000-0001-7904-883X; ABI-6078-2020; AAJ-1027-2021; ABB-7580-2020; AAK-3371-2021; AAH-3843-2020; AAH-1420-2021; F-8554-2017; AAE-1069-2022; 55390409800; 6508156530; 37088030300; 50261655300; 6602965754; 55665145000; 25650627600; 55901306600; 8347194000; 6602156436; 7006207332; 6603942124Background: Thymomas and thymic carcinomas are rare malignancies and devising clinically effective molecular targeted therapies is a major clinical challenge. The aim of the study was to analyze BLC2 and vascular endothelial growth factor receptor (VEGFR) expression and KRAS and EGFR mutational status and to correlate them with the clinical characteristics of patients with thymomas and thymic carcinomas. Materials and Methods: A total of 62 patients (mean age: 50.4 +/- 13.2 years) with thymomas and thymic carcinomas were enrolled. The expression of BLC2 and VEGFR in tumor cells and normal tissues was evaluated by RT-PCR. The mutational status of the KRAS and EGFR genes was investigated by PCR with sequence specific primers. Results: The BLC2 and VEGFR expression levels did not differ significantly between tumor and normal tissues. Moreover, there were no clearly pathogenic mutations in KRAS or EGFR genes in any tumor. None of the molecular markers were significantly related to clinical outcomes. Conclusions: Changes in levels of expression of BLC2 and VEGFR do not appear to be involved in thymic tumorigenesis. Moreover, our data suggest that KRAS and EGFR mutations do not play a major role in the pathogenesis of thymomas and thymic carcinomas.Item The mutation spectrum of the APC gene in Turkish patients with familial adenomatous polyposis(Lippincott Williams & Wilkins, 2007-11) Zorluoğlu, Abdullah; Tunca, Berrin Türkei; Çeçener, Gülşah; Egeli, Ünal; Yılmazlar, Tuncay; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Genel Cerrahi Anabilim Dalı.; 0000-0001-7904-883X; 0000-0002-1619-6680; 0000-0002-3820-424X; AAH-1420-2021; ABI-6078-2020; AAP-9988-2020; 6602965754; 6508156530; 55665145000; 6701800362Purpose: Familial adenomatous polyposis, an autosomal-dominant disease characterized by the presence of 100 or more colorectal adenomatous polyps, results from mutations in the adenomatous polyposis coli tumor suppressor gene. This study was designed to investigate adenomatous polyposis coli gene mutations in members of Turkish families with familial adenomatous polyposis to constitute an adenomatous polyposis coli mutation spectrum for the Turkish population and to determine specific biomarkers for use in the early diagnosis of familial adenomatous polyposis. Methods: We investigated adenomatous polyposis coli gene mutations in six unrelated families with familial adenomatous polyposis by using heteroduplex analysis and DNA sequencing. Results: We identified three different mutations in six families. Of these one is known and two are novel: 1018T > C and 1309delGAAAA. The mutation of a T to C transversion at codon 1018 does not cause an alteration in the meaning of the codon; however, it was determined that this silent mutation does cause the formation of new exonic splicing enhancers (ESEs) motifs on a mutated sequence by using ESEfinder program. Conclusions: This study contributes to enlarging the adenomatous polyposis coli gene mutations spectrum and to defining new biomarkers for the early diagnosis of Turkish patients with familial adenomatous polyposis.Item Overexpression of CK20, MAP3K8 and EIF5A correlates with poor prognosis in early-onset colorectal cancer patients(Springer, 2013-04) Zorluoglu, Abdullah; Tunca, Berrin Türkei; Tezcan, Gülçin; Çeçener, Gülşah; Egeli, Ünal; Yılmazlar, Tuncay; Ak, Seçil; Yerci, Ömer; Öztürk, Ersin; Umut, Görkem; Evrensel, Türkkan; Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Biyoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Genel Cerrahi Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Patoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Onkoloji Anabilim Dalı.; 0000-0002-9732-5340; 0000-0002-3820-424X; 0000-0001-7904-883X; 0000-0002-1619-6680; 0000-0002-5956-8755; AAJ-1027-2021; AAH-3843-2020; AAP-9988-2020; AAH-1420-2021; ABI-6078-2020; F-8554-2017; 6602965754; 25650627600; 6508156530; 55665145000; 6701800362; 55253485700; 6603810549; 35070171400; 37058220200; 6603942124Due to ethnic, genetic and environmental factors, the clinical and molecular characteristics of Turkish colorectal cancer (CRC) patients are different from those of Western populations. The aim of this study was to clarify the relevant alterations of gene expression associated with colorectal carcinogenesis in early-onset patients and to identify specific biomarkers that could provide novel therapeutic molecular targets in this population. The expression profiles of 114 different genes were evaluated using mRNA PCR arrays in 39 tumors and 20 surgical margin tissue samples from 39 sporadic CRC patients diagnosed at less than 50 years of age. The expression levels of IMPDH2, CK20, MAP3K8 and EIF5A were strongly up-regulated in CRC tissues compared with normal colorectal tissues (p < 0.05). The highly significant expression ratios of CK20, MAP3K8 and EIF5A observed in the colorectal tumors of patients predicted recurrence (p < 0.05). The expression of IMPDH2, CK20, MAP3K8 and EIF5A was significantly higher in the tumors of patients with short median survival (log-rank p value < 0.05). Progression-free survival was also significantly increased in patients with low expression of the EIF5A gene compared with those who exhibited high expression of this gene (log-rank p value < 0.05). We demonstrated that high CK20, MAP3K8 and EIF5A expression levels were significant prognostic factors for poor overall survival in CRC patients. Further studies and validations are required; these genes may provide novel therapeutic molecular targets for CRC treatment, as well as new directions for the development of anticancer drugs.Item Overexpression of miR-21 Is Associated With Recurrence in Patients With Hepatitis B Virus-Mediated Hepatocellular Carcinoma Undergoing Liver Transplantation(Elsevier, 2019-05) Dündar, Halit Ziya; Aksoy, Fuat; Aksoy, Seçil Ak; Taşar, Pınar; Uǧraş, Nesrin; Tunca, Berrin Türkei; Egeli, Ünal; Çeçener, Gülşah; Yerci, Ömer; Kaya, Ekrem; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Cerrahi Tıp Bilimleri/Genel Cerrahi Bölümü.; 0000-0001-5808-9384; 0000-0002-1619-6680; 0000-0002-3820-424X; 0000-0001-7904-883X; HII-8895-2022; ABI-6078-2020; AAP-9988-2020; AAH-2716-2021; AAH-1420-2021; 55453773300; 57208705658; 57193933334; 57208702845; 55386535600; 6602965754; 55665145000; 6508156530; 6603810549; 7004568109Liver transplantation (LT) is the best treatment option for hepatitis B virus (HBV)e mediated hepatocellular carcinoma (HCC). Nevertheless, recurrence is the most important issue after LT. The aims of the present study were to evaluate the relation of dysregulated expression of microRNAs (miRNAs) in recurrence formation in HBV-mediated HCC cases. A total of 42 HBV-mediated HCC patients were evaluated in this study. Among 21 miRNAs, the expression level of miR-106a and miR-21 were higher and miR-143 and miR145 were lower in patients with HCC compared with noncancerous liver tissues (P = .0388, P = .0214, P = .0321, and P = .002, respectively). Compared with nonrecurrent patients, the expression level of miR-21 was 3.54-fold higher and miR-145 was 2.42-fold lower in patients with recurrence during the 5-year follow-up (P = .004 and P = .032; respectively). In addition, according to multivariate Cox regression analysis, the overexpression of miR-21 was found to be a prognostic indicator in HBV-mediated HCC patients (P = .002). In conclusion, we show a significant association between high expression of miR-21 and recurrence in HBV-mediated HCC. Therefore, up-regulation of miR-21 could serve as a promising prognostic marker for HCC.Item Triple negative breast cancer: New therapeutic approaches and BRCA status(Wiley, 2018-04-25) Güney Eskiler, Gamze; Çeçener, Gülşah; Egeli, Ünal; Tunca, Berrin Türkei; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı.; 0000-0002-3820-424X; 0000-0001-7904-883X; 0000-0002-1619-6680; AAP-9988-2020; AAH-1420-2021; ABI-6078-2020; 6508156530; 55665145000; 6602965754Treatment of triple negative breast cancer (TNBC) is a clinically challenging problem due to intriguing clinical and pathologic features of TNBC and natural or induced resistance to existing therapies. However, a great understanding of features of TNBC particularly associated with BRCA mutations has led to the development of different therapeutic approaches. Besides, identification of TNBC subtypes contribute to investigation of the underlying molecular differences and development of new strategies for the treatment of TNBC patients. In this review, we discussed the definition and characteristic properties of TNBC. We summarized an up-to-date description of the reported clinical trials of novel targeted strategies especially PARP inhibitors (PARPi) due to novel and highly potent for the treatment of TNBC. Additionally, we reviewed published studies which investigated the prevalence and types of BRCA1/2 mutation in breast cancer patients to assess and draw attention of association of BRCA status with TNBC. Consequently, the definition subtype of TNBC has important predictive value for the development of new therapeutic agents in the treatment of TNBC. Additionally, the incidence and types of mutations in BRCA-related pathways may be affected by ethnic origin and contribute to the risk of developing TNBC.