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Objectives 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

Amaç: Nükleer tıpta radyonüklit tedavilerde çalışan radyasyon görevlilerinin uzun dönemde maruz kaldığı radyasyon dozlarının belirlenmesi ve rutin olarak yapılan her bir tedavi prosedürünün bu dozlara katkısının belirlenmesi amaçlanmıştır. Gereç ve Yöntem: 6 yıl boyunca rutin olarak İyot-131 (131I) tedavisi, (Lutesyum-177 (177Lu) tedavisi, Yittrium-90 (90Y) mikrosfer tedavisi ve 131I MIBG (Meta-İyodobenzilguanidin) tedavisi uygulayan doktor, hemşire, sağlık fizikçisi, radyofarmasist ve temizlik personelinin kişisel dozimetri kayıtları geriye dönük olarak incelendi. Aynı dönemde gerçekleştirilmiş olan tedavi sayıları ve bu tedavilerde görevli olanlar belirlendi. Bu bilgilerden radyasyon görevlilerinin tedavilerdeki absorbe radyasyon dozları ile prosedür başına doz değerleri çıkarıldı. Bulgular: Yıllık ortalama radyasyon dozları en yüksek radyofarmasistlerde 2185±1839 µSv bulundu. Hemşirelerde 786±943 µSv, sağlık fizikçilerinde 753±706 µSv, doktorlarda 626±741 µSv ve temizlik görevlisi personellerde 961±1099 µSv olarak hesaplandı. Prosedür başına hesaplanan ortalama doz değerleri en yüksek doktorlarda 129±208 μSv olarak bulundu. Hemşirelerde 122±187 μSv, sağlık fizikçilerinde 76±122 μSv, radyofarmasistlerde 76±52 μSv, temizlik görevlisi personellerde 42±64 μSv bulundu. Sonuç: Radyofarmasötiklerin hazırlanması sırasında, hastaya uygulanması sırasında ve hastanın tedavi servisinde yattığı süre boyunca doz aşımı olmamış, belirlenen radyasyon dozlarının izin verilen güvenli değerlerde olduğu tespit edilmiştir.

Background: Familial Mediterranean fever (FMF) is an autoinflammatory disease. Because FMF commonly affects people of childbearing ages, the effect of the disease and its treatment on fertility and pregnancy outcomes is under consideration. This study aimed to evaluate pregnancy outcomes and contraception methods of FMF patients. Results: The records of 62 female FMF patients were retrospectively evaluated. Intrauterine devices and tubal ligation are the most common contraception methods. Of the 62 patients, 25 patients had 39 pregnancies. Of the 39 pregnancies, miscarriages were miscarriage, two had abortus, one was ectopic, and the remaining 26 were delivered. Two of the deliveries were preterm and the remaining were term. All patients received colchicine treatment, and the dose of colchicine had no effect on the pregnancy results (chi-square: 5.475, p = 0.708). Conclusion: Colchicine treatment is safe during pregnancy. Furthermore, having FMF or receiving colchicine therapy does not affect the contraception habits of patients.

The aim of the study was to investigate the frequency and types of mutations on the RB1 gene at the familial, clinical, and ethnic levels which are known to have an important role in the genetics of retinoblastoma in Turkish population. RB1 gene mutation analysis was performed in 219 people (122 probands, 14 family members with retinoblastoma and 83 clinically healthy family members) in total. All 27 exons and close intronic regions of the RB1 gene were sequenced for small deletions and insertions using both the Sanger sequencing or NGS methods, and also the large deletions and duplications were investigated by both the Multiplex Ligation Probe Amplification (MLPA) analysis and the Copy Number Variation (CNV) algorithm. The general RB1 gene mutation frequency of the patients with retinoblastoma was 41.9%. The bilateral retinoblastoma rate was 34.5% in our study population. It was striking that approximately 51.5% of our patients were diagnosed 12 months earlier, and de novo mutation occurred in 90.4% of the patients. Small genetic rearrangement mutations were detected in 78.9% of patients and Large Genetic Rearrangement (LGR) was detected in 21.1% of patients. There was a relationship between the eye color of the RB patients and RB1 mutations. As a conclusion, the familial, clinical and ethnical level of the RB1 gene mutations which are known to have a significant role in genetics of retinoblastoma were investigated, and different RB1 mutations, 10 of which are novel, have been identified on the RB1 gene sequence.

The climate-induced increase in precipitation extremes leads to more frequent combined sewer overflows (CSOs) from wastewater treatment plants into urban rivers, which are often used for recreation. This study simultaneously investigates the changes in precipitation extremes, CSO frequency and volume, the resulting fecal microbial loads to streams, and the human infection risks during recreational use.Our model approach consists of four steps. First, a disaggregation model is used to increase the temporal resolution of the 22 climate scenarios used to cope with the dynamics of urban hydrological processes. Then, continuous simulations are performed using an urban hydrological model (SWMM) for the C20 period (1971-2000), the near-term future (2021-2050), and the long-term future (2071-2100). We simulated the microbial load of the combined sewer discharge with the fecal indicators E. coli, C. perfringens, a human-associated genetic fecal marker HF183/BacR287, and the pathogens Giardia and Cryptosporidium spp. To determine the dilution in the stream, rainfall-runoff modeling is performed using a conceptual semi-distributed hydrological model in the third step for the urban catchment towards the point of CSO discharge. In the final step, a quantitative microbial risk assessment (QMRA) is performed to quantify the potential human infection risks during recreational use.A hypothetical urban drainage system serves as the study area, which was adapted to the local conditions of a subarea of the city of Vienna including a receiving river. For the precipitation extremes, average increases in precipitation of 13 % for the near future and 19 % for the long-term future are determined over the 22 climate scenarios and 5 rainfall stations considered (extreme event durations 5 min to 24 h, recurrence intervals 0.33 yrs to 10 yrs).The increase in precipitation extremes results in a higher number of CSOs for both the near- and long-term future. The simulated discharge of the receiving river is often still unaffected by the rainfall event at the time of discharge due to the concentration-time of the catchment, resulting in no direct relationship between discharge and CSO. A realistic estimate of the microbial load discharges during extreme rainfall events is possible for the first time based on the simultaneous continuous hydrological and urban hydrological models in this study.The resulting concentrations of E. coli, C. perfringens, HF183/BacR287, Giardia, and Cryptosporidium spp. in the receiving water as well as the potential infection risks are analyzed separately on a seasonal and annual basis. For both pathogens, infection risks in the distant future are found to increase in all seasons, with lower increases in the winter months (December-February) than in the rest of the year. The highest risk of infection is found in autumn (September-November).

The Fibulins are a recently discovered family of extracellular matrix proteins. In this study, expression levels of the fibulin-2 (FBLN2) gene and its role in the formation of different metastatic foci were investigated in lung cancer patients. We analyzed 106 lung cancer patients and eight paraffin-embedded tissues, and 27 ethnical-, age- and sex-matched healthy controls for expression levels of the FBLN2 gene. cDNAs obtained from the enriched epithelial cells of peripheral blood lymphocytes and tumor tissues of patients were amplified with specific primers for the target FBLN2 gene and HPRT1 housekeeping gene using quantitative real-time polymerase chain reaction. FBLN2 gene expression levels of the enriched epithelial cells of peripheral blood lymphocytes were found to be decreased approximately twofold in all subsets of patients compared to healthy controls. Our results indicate a significant difference between patient subgroups and controls [F(4.124) = 14.846, p0.05] among patient subgroups: bone metastases versus non-metastatic groups (p = 0.997), bone versus brain metastases (p = 0994), bone metastases versus two primary tumors (p = 0.999), brain metastases versus two primary tumors (p = 0.999), brain metastases versus non-metastatic (p = 0.755), non-metastatic versus two primary tumors (p = 0.996), non-metastatic versus all other metastatic patients (p = 0.731). Moreover, we found a 50-fold upregulation of FBLN2 gene expression in paraffin-embedded tissues compared with the enriched epithelial cells of peripheral blood lymphocytes of patients. In the study, the enriched epithelial cells of peripheral blood lymphocytes of decreased FBLN2 expression was found to be correlated with metastasis. The fibulin-2 molecules might induce the metastatic potential through interaction with the other molecules in the microenvironment, nevertheless, it is needed further research whether the importance of FBLN2 on lung cancer oncogenesis and as a biomarker for metastatic lung cancer.

e22007 Background: Retinoblastoma (RB) is the most common intraocular malignancy in children, caused by mutations in the tumor suppressor RB1 gene. Patients with bilateral/trilateral/familial RB are considered to have hereditary RB (1 germline, 1 somatic mutation); although most unilateral RB are nonhereditary (2 somatic mutations), some have germline RB1 mutation. Identification of RB1 mutations and genetic counseling is essential to assess the risk of developing RB in the patients´ relatives and to prevent the disease. The aim of this study is to assess the frequency/type of RB1 gene mutations in a large cohort of Turkish RB cases. Methods: RB1 gene mutation screening was performed in peripheral blood samples of 219 individuals (122 children with RB/14 family members with RB/83 healthy family members of 47 probands with RB1 mutations) followed in the Istanbul University, Oncology Institute. All 27 exons and close intronic regions of the RB1 gene were sequenced for small deletions and insertions using the Sanger sequencing (2013-2018) or Next Generation Sequencing (2019-2021); large deletions and duplications were investigated both by Multiplex Ligation Probe Amplification (MLPA) and copy number variation (CNV). Correlation with demographic and clinical data were evaluated. Results: After RB1 mutation screening, mutations were detected in 57 (41.9%) of 136 patients. RB1 mutations was observed in 23/84 (27.4%) patients with unilateral RB, in 30/47 (63.8%) bilateral RB, in 3/3 trilateral RB, and1/2 unilateral retinoma. Of these mutations, 45 (78.9%) were small genetic rearrangements and 12 (21.1%) large genetic rearrangements. Frameshift mutations were found in 11, nonsense in 18, splice error in 11, and missense mutation in 1, synonymous substitution in 2, upstream substitution in 2 patients. Ten novel mutations were found. Three of 83 healthy family members also had germline RB1 mutation. The disease was hereditary in 13 (22.8%); and de novo (77.2 %) in 44 of the 57 patients with mutations. Three siblings were found to have RB1 mutation, while their parents did not. Patients diagnosed as infants (RB1 mutation found in 63.2% of 70 infants vs in 36.8% of older ones, p:0.021); those with bilateral/trilateral RB (66 vs 27.4%, p:0.0001); those with light (green-blue) iris color vs dark color (71.4% vs 36.5%. p:0.003) had higher frequency of RB1 gene mutation. There was no significant correlation regarding gender or ICRB stage and RB1 mutation frequency. Conclusions: RB1 gene mutation was found in 41.9% of Turkish children with RB, in 63.8% of bilateral and 27.4% of unilateral RB. 10 novel mutations of the RB1 gene were found according to the Leiden Open Variation Database and the Human Gene Mutation Database.The mutation frequency was significantly higher in patients with bilateral/trilateral RB, in infants, in those with light iris color. In bilateral RB with no RB1 mutation, other genes/RB1 gene methylation and expression status may play a role in the pathogenesis.

Background The most common cancers detected in women are breast, thyroid, colorectal, uterine corpus, lung, and ovarian cancer. Ovarian cancer is responsible from more than 150.000 death annually worldwide. This cancer is detected in the late stage, and is characterised with poor prognosis, therefore most cases result with death. The fact that this cancer manifests itself in the late stage and is characterized by a poor prognosis, is caused death in the majority of cases. Therefore, the diagnosis and the treatment of the disease have to be improved for a better quality of life for patients. MicroRNAs are the noncoding RNAs in the length of 19–24 nucleotides which show suppressor effect on target genes. miRNAs are included in the pathology of various diseases including cancer. miRNAs being as the biomarker candidates in diagnosis, and their use in treatment as the inhibitors of the molecules mimicking the miRNA showed that they may be used as the new therapeutic target and agents. Methods We detected with our group in our prior study conducted with disconcordant ovarian cancer twins that many miRNA molecules were different in ovarian cancer compared with the molecules in healthy sibling. The expression level of miR-142-3p that was selected from the miRNAs detected in the previous study was compared, and investigated in a wider ovarian cancer group, and in healthy control group. miR-142-3p expression level was investigated using the real-time PCR method in the present study involving 147 patients, and 100 healthy control group. The differences in the expression levels of miR-142-3p detected in the peripheral blood lymphocytes of ovarian cancer patients, and healthy control were statisticaly evaluated. Results The expression level of miR-142-3p was detected to have increased 3.11 fold in ovarian cancer patients compared with the levels in healthy controls, and the difference was statistically significant (p:0.00). These results suggest that miR-142-3p that was found significantly increased in the peripheral blood samples of ovarian cancer patients compared with the healthy controls might be used as a sensitive, noninvasive biomarker in the early diagnosis, and treatment and follow up of ovarian cancer.

BRCA1/2 gene testing is a difficult, expensive, and time-consuming test which requires excessive work load. The identification of the BRCA1/2 gene mutations is significantly important in the selection of treatment and the risk of secondary cancer. We aimed to develop an algorithm considering all the clinical, demographic, and genetic features of patients for identifying the BRCA1/2 negativity in the present study. An experimental dataset was created with the collection of the all clinical, demographic, and genetic features of breast cancer patients for 20 years. This dataset consisted of 125 features of 2070 high-risk breast cancer patients. All data were numeralized and normalized for detection of the BRCA1/2 negativity in the machine learning algorithm. The performance of the algorithm was identified by studying the machine learning model with the test data. k nearest neighbours (KNN) and decision tree (DT) accuracy rates of 9 features involving Dataset 2 were found to be the most effective. The removal of the unnecessary data in the dataset by reducing the number of features was shown to increase the accuracy rate of algorithm compared with the DT. BRCA1/2 negativity was identified without performing the BRCA1/2 gene test with 92.88% accuracy within minutes in high-risk breast cancer patients with this algorithm, and the test associated result waiting stress, time, and money loss were prevented. That algorithm is suggested be useful in fast performing of the treatment plans of patients and accurately in addition to speeding up the clinical practice. Scientific Research Projects Coordination Unit of Istanbul UniversityIstanbul University [TSA-2019-34244] This study was funded by the Scientific Research Projects Coordination Unit of Istanbul University (project number: TSA-2019-34244).

MicroRNAs (miRNAs), are endogenous noncoding single strand RNA molecules with approximate length of 22 nucleotides. Ovarian cancer is a heterogenous disease which includes different biologic behaviors in the clinical, and molecular level. miRNAs have roles in the early diagnosis, prognosis, and chemotherapy sensitivity for ovarian cancer, and in the regulation of reproduction by being expressed in the ovaries. The expression level of two miRNAs of miR-423-5p, and miR-664b-5p selected from the miRNAs which were detected to be important for the ovarian cancer etiology in our previous studies were investigated in the peripheral blood of familial and sporadic ovarian cancer patients, and in healthy individuals. The expression analyses were statistically evaluated with SPSS v21.0 program using the Quantitative Real-Time PCR technique. A statistically significant difference was detected for both miRNAs between the healthy controls and ovarian cancer patient groups (p:0.000). The miR-423-5p expression was detected to increase 2.35 fold, and miR-664b-5p was detected to increase 2.47 fold in ovarian cancer patients compared with the levels in the control group. miR-423-5p was reported to be overexpressed in various cancer types, and in different disease stages in previous study, and miR-423-5p was demonstrated to have increased in the lymphocytes in the peripheral circulation of ovarian cancer patients first in our literature. The miR-664b-5p expression level was detected in high levels in ovarian cancer patient group, however was detected to have decreased in 64% of ovarian cancer patients with BRCA mutation carrier. The expressions of both miRNA molecules were detected to have decreased in the ovarian cancer subgroups in patients with ovarian cancer with addition of a second primary cancer of endometrium cancer, however, were detected in the highest level in ovarian cancer patients in addition to another secondary cancer except breast and endometrium cancer. The results obtained from the study showed that the increased expression of both miRNA molecules were suggested to be associated with ovarian cancer, and decrease was suggested to be associated with endometrium cancer. In summary, the miRNA molecules in the present study might be the non-invasive biological indicator in ovarian cancer, and the demonstration of these molecules on the tumor tissue, and their change during treatment in future studies will be beneficial.

Background Ovarian cancer is the second most common gynecologic cancer with high mortality rate and generally diagnosed in advanced stages. The 5-year disease-free survival is below 40%. MicroRNAs, subset of the non-coding RNA molecules, regulate the translation in post transcriptional level by binding to specific mRNAs to promote or degrade the target oncogenes or tumor suppressor genes. Abnormal expression of miRNAs were found in numerous human cancer, including ovarian cancer. Investigating the miRNAs derived from the peripheral blood samples can be used as a marker in the diagnose, treatment and prognosis of ovarian cancer. We aimed to find biological markers for early diagnosis of ovarian cancer by investigating BRCA1 gene mutation carrier monozygotic discordant twins and their high risk healthy family individual’s miRNAs. Methods The study was conducted on monozygotic twins discordant for ovarian cancer, and the liquid biopsy exploration of miRNAs was performed on mononuclear cells that were isolated from the peripheral blood samples. The miRNA expression profile changes in the study were found by using microarray analysis. miRNA isolation procedure performed from the lymphocyte in accordance with the kit protocol. The presence and quality of the isolated miRNAs screened by electrophoresis. Raw data logarithmic analysis was studied by identifying the threshold, normalization, correlation, mean and median values. Target proteins were detected for each miRNA by using different algorithms. Results After the comparison of monozygotic discordant twins for epithelial ovarian carcinoma upregulation of the 4 miRNAs, miR-6131, miR-1305, miR-197-3p, miR-3651 and downregulation of 4 miRNAs, miR-3135b, miR-4430, miR-664b-5p, miR-766-3p were found statically significant. Conclusions The detected 99 miRNAs out of 2549 miRNAs might be used in the clinic as new biological indicators in the diagnosis and follow up of epithelial ovarian cancer with complementary studies. The miRNA expression profiles were identified to be statistically significant in the evaluation of ovarian cancer etiology, BRCA1 mutation status, and ovarian cancer risk in accordance with the obtained data. There is a need for validation of the miRNAs which were particularly detected between monozygotic twins and its association with ovarian cancer was emphasized in our study in wider cohorts including ovarian cancer patients, and healthy individuals.

MicroRNAs (miRNAs) have major roles in nearly all cellular process including gene expression, and may behave as oncogene or tumor suppressor gene by binding to complementary sequences in the target mRNA. The circulating microRNA-15a (miRNA-15a) and microRNA-16-1 (miRNA-16-1) of 15 healthy adults and of 40 untreated patients diagnosed with diffuse large B-cell lymphoma (DLBC) were recruited to investigate the expression levels. The expression levels of miRNA-15a, and miRNA-16-1 genes of the untreated DLBCL patients, and healthy individuals with matched age, sex and ethnicity were examined. MicroRNA expression profiles obtained from peripheral blood were investigated. The samples were collected from 40 patients diagnosed with DLBC patients, and from 15 healthy controls. Two miRNAs were selected, and expression profile was examined using a quantitative real-time polymerase chain reaction (qPCR) based on the previous studies. Statistically significant expression level differences (p 0.05) were detected for miRNA-16-1 in DLBCL patients and healthy control groups. miRNA-16-1 gene expression level was found approximately ninefold higher in the patient group compared to the controls; however, no statistical difference was detected in the expression profile of miRNA-15a between the both groups. On the other hand, the decreased gene expression in miRNA16-1 was observed in 88.3% of DLBCL patients. These results suggested that there was no statistically significant decrease in the miRNA-15a gene expression in DLBCL patients (p 0.05). On the contrary to the literature, miRNA-16-1 expression level was suppressed in DLBCL group in our study, however no whole gene silencing was performed. MicroRNA-16-1 might be suggested to behave as a tumor suppressor in DLBCL in our study.

Purpose. Various molecular variations are known to result in different gene variants in the FGFR4 gene, known for its oncogenic transformation activity. The goal of this study was to investigate the FGFR4 p.Gly388Arg variant that plays role in the progression of cancer and retinal growth and may be an effective candidate variant in the Turkish population in retinoblastoma patients with no RB1 gene mutation. Methods. Using the Sanger sequencing methods, the FGFR4 p.Gly388Arg variant was bidirectionally sequenced in 49 patients with non-RB1 gene mutation in retinoblastoma patients and 13 healthy first-degree relatives and 146 individuals matched by sex and age in the control group. Results. In Turkish population-specific study, the FGFR4 p.Gly388Arg variant was found in 27 (55.1 percent) of 49 patients; mutation was found in 7 (53.8 percent) of these patients’ 13 healthy relatives screened. When FGFR4 p.Gly388Arg mutation status is evaluated in terms of 146 healthy controls, in 70 (47.9 percent) individuals, mutation was observed. Our analysis showed that the FGFR4 p.Gly388Arg allele frequency, which according to different databases is seen as 30 percent in the general population, is 50 percent common in the Turkish population. Conclusions. In patients with advanced retinoblastoma who were diagnosed with retinoblastoma prior to 24 months, the FGFR4 p.Gly388Arg allele was found to be significantly higher. As a result, these results indicate that the polymorphism of FGFR4 p.Gly388Arg may play a role in both the development of tumors and the progression of aggressive tumors.

Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal cancers. Known risk factors for this disease are currently insufficient in predicting mortality. The only FDA approved prognostic biomarker for PDAC patients is CA19-9. This, along with AJCC TNM staging and performance status, are considered important prognostic indicators in clinical practice. In order to better prognosticate patients with PDAC, we identified a novel panel of genes by utilizing publically available microarray and RNAseq data of PDAC tumors from GEO and TCGA. Expression of 20 genes were significantly associated with overall survival in four datasets and event-free survival in TCGA. A score generated based on the expression matrix of these genes could be validated in two independent cohorts. We find that this “Pancreatic cancer prognostic score 20 – PPS20” is dramatically elevated in metastatic tissue compared to primary tumor, and is higher in primary tumors compared to normal pancreatic tissue. Transcriptomic analyses show that tumors with low PPS20 have overall more immune cell infiltration and a higher CD8 T cell/Treg ratio when compared to those with high PPS20. Analyses of proteomic data from TCGA PAAD indicated higher levels of Cyclin B1, RAD51, EGFR and a lower E-cadherin/Fibronectin ratio in tumors with high PPS20. The PPS20 score defines not only prognostic and biological sub-groups but can predict response to targeted therapy options as well. Overall, PPS20 is a stronger and more robust transcriptomic signature when compared to similar, previously published gene lists.

Additional file 2. BRCA1 mutation carriage and epithelial ovarian cancer etiology related upregulated and downregulated miRNAs, target molecules.

Additional file 1. BRCA1 gene mutation positivity related upregulated and downregulated miRNAs and target molecules.

Ovarian cancer is a disease that is generally diagnosed at an advanced stage, and has poor survival. Monozygotic (MZ) twins are considered to be good research models for investigating the epigenetic changes associated with diseases. In the present study, the involvement of epigenetic mechanisms in ovarian cancer etiology were evaluated using the MZ twin model. Whole-genome methylation patterns were investigated in a BRCA1 gene mutation-carrying family comprising MZ twins, only one of whom had ovarian cancer, and other healthy siblings. Whole-genome methylation patterns were assessed in peripheral blood DNA using Infinium MethylationEPIC BeadChips on an Illumina iScan device. The hypermethylated and hypomethylated genes were detected between cases and controls in four different comparison groups in order to evaluate the differences in methylation levels according to cancer diagnosis and BRCA mutation status. The obtained results showed that the differential methylations in 12 different genes, namely PR/SET domain 6, cytochrome B5 reductase 4, ZNF714, OR52M1, SEMA4D, CHD1L, CAPZB, clustered mitochondria homolog, RB-binding protein 7, chromatin repair factor, ankyrin repeat domain 23, RIB43A domain with coiled-coils 1 and C6orf227, were associated with ovarian cancer. Biological functional analysis of the genes detected in the study using the PANTHER classification system revealed that they have roles in biological processes including 'biologic adhesion', 'regulation', 'cellular components organization', 'biogenesis', 'immune system functioning', 'metabolic functioning' and 'localization'. Overall, the present study suggested that epigenetic differences, such as methylation status, could be used as a non-invasive biological markers for the early diagnosis and follow-up of ovarian cancer. © 2020 Spandidos Publications. All rights reserved. Istanbul Üniversitesi: 59477 This study was supported by the Scientific Research Projects Unit of Istanbul University (project no. 59477). In the study, the funding body has no role in the preparation, data collection, analysis and interpretation of the manuscript.

Additional file 3. Epithelial ovarian cancer predisposition associated upregulated and downregulated miRNAs, target molecules.

Objective The current rearrangement ratio of BRCA1 and BRCA2 genes is not known in the Turkish population. Rearrangements are not routinely investigated in many Turkish laboratories. This creates problems and contradictions between clinics. Therefore, the aim of this study was to evaluate the distribution and frequency of rearrangements in BRCA1 and BRCA2 genes in high-risk families and to clarify the limits of BRCA1 and BRCA2 testing in Turkey. Materials and Methods The study included 1809 patients at high risk of breast cancer or ovarian cancer. All patients were investigated for both small indels and rearrangements of BRCA genes using DNA sequencing and multiplex ligation-dependent probe amplification (MLPA) analysis. Results The overall frequency of rearrangements was 2% (25/1262). The frequency of rearrangements was 1.7% (18/1086) and 4% (9/206) in patients with breast cancer and ovarian cancer, respectively. The frequency of rearrangements was 3.7% (8/215) in patients with triple-negative breast cancer. The rearrangement rate was 7.7% (2/26) in patients with both breast and ovarian cancer. Conclusions Rearrangements were found with high rates and were strongly associated with bilateral and triple-negative status of patients with breast cancer, which are signs of high risk for breast and ovarian cancer. Analysis of rearrangements should definitely be included in routine clinical practice in Turkey for high-risk families and also for improved cancer risk prediction for families.

Amaç: Bu çalışmada Romatoloji Polikliniğine başvuran RA’lı hastalarda alerjik hastalıkların sıklığı ve hastalık aktivitesi ile olan ilişkisinin değerlendirilmesi etweenMateryal ve Metot: Hastalara, sosyodemografik veri formu ve “Avrupa Topluluğu Solunum Sağlığı Çalışması” (European Community Respiratory Health Study, ATSSÇ) anketi uygulanarak alerjik hastalıkların yaygınlığı ile RA hastalık aktivitesi (DAS-28) arasındaki ilişki saptanmaya çalışılmıştırBulgular: Toplam 135 hasta çalışmaya alındı (108 kadın 27 erkek; yaş ortalaması 53,0±11,1 yıldı). Kadınların %33,3’ünde astım benzeri bulgular görülmüştür. Erkeklerin %33,3’ünde astım benzeri bulgular ve %33,3’ünde non enfeksiyöz rinit görülmektedir. DAS-28 skoru ile anket tanılarının sıklığı arasında istatistiksel olarak anlamlı bir fark bulunamamıştır( p=0,75).Sonuç: Çalışmamızda RA aktivite skoru ile ATSSÇ tanıları arasında anlamlı bir ilişki bulunmadı. Literatür taramamızda; RA hastalarında DAS-28 ile alerjik hastalık ilişkisini araştıran bir çalışma bulamadık. Bu nedenle bu sonucun önemli olduğu kanaatindeyiz., Objectives: We aimed to assess the relationship between disease activity and frequency of allergic diseases in patients with rheumatoid arthritis who were admitted to a rheumatology outpatient clinic.Materials and methods: Socio-demographic data form and the European Community Respiratory Health Study (ECRHS) questionnaire were applied to the patients and the prevalence of allergic patients by applying ECHRS and the relationship between RA disease activity was assessed.Results: A total of 135 patients were included in the study (108 female and 27 male); average age 53,0 ± 11,1 years. Asthma-like symptoms were observed in 33,33% of women. Asthma-like symptoms in 33,33% of men and 33,33% are non-infectious rhinitis. A statistically significant difference was not found between DAS-28 scores and frequencies of the survey diagnoses (p = 0,75).Conclusion: We could not find a significant correlation between the diagnosis of RA activity score and ECHRS diagnoses in our study. We could not find a study which focused on the relationship between allergic diseases and DAS-28 in RA in the literature. Thus, we believe that these results are noteworthy

Background:The causes of hereditary breast cancer are classified in two groups as modifiable and non-modifiable (genetic) in our study.Some of the non-modifiable factors selected are breast density, menarche age, menopause, BRCA1 and BRCA2 genes, family history, height and weight of patients.On the other hand, oral contraceptive usage, alcohol consumption, hormone therapy, breastfeeding, exposure to radiation and smoking are among the modifiable factors.The risk of having hereditary breast cancer could be identified by BRCA1/BRCA2 gene tests which requires long lasting experiments and incurs high costs. Before performing the required genetic test, the modifiable and non-modifiable factors of the high risk patients are collected by geneticist or genetic counselor and then calculated risk score of the patients.After observing the test results, the effect of existing factors are analyzed.The aim of this study is to develop a hereditary breast cancer prediction algorithm by using data mining techniques for high risk breast cancer patients.Methods:Different applications may require different data mining methods.The current study involves the data classification technique for predicting hereditary breast cancer through a function that incorporates modifiable and non-modifiable factors. The data consists of 562 BRCA negative, and 68 BRCA positive instances with 117 categorical and numerical characteristics.The first step of this approach is preprocessing the data on hand.Individuals with incomplete data are excluded from the list, and some logical adjustments are performed.Results:As a result, 440 patients (392 BRCA negative, 48 BRCA positive), and 75 characteristics (3 numerical, 72 categorical attributes) are obtained.In the second step, important factors are determined by attribute selection algorithms. After applying 23 selection and 7 ranking methods, the important attributes are determined as: age, diagnosis, height, weight, menopause age, menarche age, FIB/FIB40, SEO, cancer status of the family, clinical stage, and pathological stage.As a result, three data sets are suggested for classification. Finally, a total of 182 data classification results are derived for the aforementioned data sets.All analyses are performed by employing WEKA software.Conclusion:Comparison of the results shows that, the best data classification method's predictions on the BRCA negative class has 100% accuracy.Hence, a new individual's situation can be assessed without undergoing detailed gene tests, resulting in cost and required workforce reduction.The results are found to be promising and applicable.As an extension of the study, a user friendly interface and a decision support tool can be developed. Citation Format: Seda Kilic, Ozge Sukruoglu, Demet Akdeniz, Mukaddes Avsar, Bugra Tuncer, Şimal Aysever, Suzan Güreli, Fadime Üney-Yüksektepe, Tulin Aktin, Hulya Yazici. Selection of BRCA1/2 negative cases using data mining analytical approach for hereditary breast cancer prediction in high risk breast cancer patients. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3741. doi:10.1158/1538-7445.AM2015-3741

Background: The distribution of hereditary breast and ovarian cancer in Turkish population has been reported in earlier publications. However, the regional distributions of breast cancer and/or BRCA1/2 gene mutations frequency are not known for Balkan Turks who came to Turkey for the forced migration in 1989 and for general Turkish populations in Turkey. Materials and Method: We recruited 401 patients with a family history of breast and/or ovarian cancers, and 126 early-onset breast cancer cases below age 40 with/without a family history of cancer between 1994-2013. These patients were referred to Cancer Genetics Department of Oncology Institute in University of Istanbul. Families were selected from consecutive referrals to the above-listed hospital meeting specific family-history criteria (either multiple cases of breast and or ovarian cancer in the family or the presence of an individual with a young age at diagnosis). Mean age of patients in the study was 41, 18±10, 24. Results: The distributions of patients participating in the study were evaluated in total 8 groups such as seven geographic regions of Turkey and the Balkan Turks. Overall frequency of BRCA1/2 gene mutations in Turkish population was 10%. The distribution of patients according to 8 groups were 26.6% in the Black Sea Region, 21.5% in the Marmara Region, 17.6% in the Eastern Anatolia Region, 8.6% in Central Anatolia, 3.1% in Aegean Region, 3.9% in the Mediterranean region, 2.7% in South Eastern Anatolia and 16% in Balkan Turks. BRCA1 and BRCA2 positivity was evaluated in the study groups: BRCA1/2 mutations ratio were 20% in the Black Sea Region, 16% in the Marmara Region, 20% in the Eastern Anatolia Region, 12% in Central Anatolia, % 4 in Aegean Region and 28% in the Balkan Turks. None of mutations in both genes were found in the patients participating in the study from South Eastern Anatolia and the Mediterranean regions. The observed BRCA1/2 mutations rate was found almost two-fold according to the expected mutation rate in the group of Balkan Turks. The highest breast cancer rates were seen in the city of Giresun in the Black Sea Region and in the city of Malatya in the Eastern Anatolia Region, respectively. Conclusions: In our study, breast cancer was more frequent in the regions which were the Black Sea, the Marmara, Eastern Anatolia and the Balkan Turks group. Although the Marmara region was industrialized, Bulgaria where Balkan Turks lived before forced-migration and the Black Sea Region are not industrialized areas. However, in 1986, these regions were the most affected by the Chernobyl disaster and these interactions was described with scientific data. Therefore, it might be concluded that the high rates of breast cancer are associated with the Chernobyl disaster in these regions. In the study, BRCA1/2 gene mutation rates were examined in Balkan Turks who came to Turkey by forced-migration after Chernobyl disaster. In the group of Balkan Turks, almost two fold expected incidence for BRCA1/2 gene mutations was observed. The investigated society was a small community living as a minority in Bulgaria. Therefore, it was suggested that the society was isolated as a nature and has been had high BRCA1/2 mutations rate. On the other hand, in the study, BRCA1/2 gene mutations and clinical/pathological data were also compared and survival analysis was performed in the general Turkish population. The diagnosis age for breast cancer was found 10 years earlier when compared to the other populations (p Citation Format: Demet Akdeniz, Bugra S. Tuncer, Seda Kilic, Ozge Sukruoglu, Leyla Kilic, Kevser Altundag, Rumeysa Ciftci, Sevda Ozel, Senem Karabulut, Meltem Ekenel, Pinar Saip, Hasan Karanlik, Neslihan Cabioglu, Hulya Yazici. Distribution and frequency of BRCA gene mutations in Turkish population including Balkan Turks. [abstract]. In: Proceedings of the AACR Special Conference: Cancer Susceptibility and Cancer Susceptibility Syndromes; Jan 29-Feb 1, 2014; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(23 Suppl):Abstract nr 43. doi:10.1158/1538-7445.CANSUSC14-43

e19533 Background: MicroRNAs (miRNA) are 21-23 nucleotide-long single-stranded RNA molecules that are not converted to proteins. Mature miRNA molecules show partial complementation to a part of one...

e16526 Background: Mutations in the BRCA1 and BRCA2 genes confer greater risk of developing ovarian cancer. We determined the regional distributions of ovarian cancer and BRCA1/2 gene mutations fre...

e19130 Background: The Fibulins are a recently discovered family of ECM proteins.In this study, expression levels of the fibulin-2 (FBLN2) gene in lung cancer patients and its role in the formation...