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Assisted reproduction technology has two significant problems: low success rates and multiple pregnancies. Because of these problems, the priority in IVF clinics is to develop a potential diagnostic test that can be used to select the embryos with the ultimate developmental competence. Aneuploidy screening as embryo selection criteria will ensure that the transferred embryos are euploid and high implantation rate. We hypothesize that aneuploidy in human preimplantation embryos could be discriminated by their amino acid metabolism profile in the spent culture media. Preimplantation genetic testing for aneuploidy results and spent embryo culture medium amino acid content were analyzed for 58 couples. The nextgeneration sequencing technique was used and coupled with TE biopsy. Forty euploid and 71 aneuploid blastocysts were evaluated. Embryos were cultured individually until day 5 or 6 of embryo development. Spent culture medium was collected after finishing the culture. There was no statistical difference between D3 and D5 embryo morphology between euploid and aneuploid embryos (p > .05). Eight amino acids, including SER, GLY, HIS, ARG, THR, ALA, PRO, and TYR, were detected in the culture medium from the blank control group, euploid group, and aneuploid group. Only TYR amino acid concentration was found significantly higher in the aneuploid group compared to the euploid group (p < .003). Tyrosine amino acid levels equal to and above 76.38 mmol/L could be considered aneuploid. Aneuploid embryos demonstrate altered amino acid turnover in vitro relative to euploid counterparts. A noninvasive method of amino acid profiling will be of value as a tool for routine preimplantation embryo selection among all patient groups.

Background There is a growing interest in noninvasively defining molecular subsets of hemispheric diffuse gliomas based on the isocitrate dehydrogenase (IDH) and telomerase reverse transcriptase gene promoter (TERTp) mutation status, which correspond to distinct tumor entities, and differ in demographics, natural history, treatment response, recurrence, and survival patterns. Purpose To investigate whether metabolite levels detected with short echo time (TE) proton MR spectroscopy (1 H-MRS) at 3T can be used for noninvasive molecular classification of IDH and TERTp mutation-based subsets of gliomas. Study type Retrospective. Subjects In all, 112 hemispheric diffuse gliomas (70 males/42 females, mean age: 42.1 ± 13.9 years). Field strength/sequence Short-TE 1 H-MRS (repetition time (TR) = 2000 msec, TE = 30 msec, number of signal averages = 192) and routine clinical brain tumor MR protocols were acquired at 3T. Assessment 1 H-MRS data were quantified using LCModel software. TERTp and IDH1 or IDH2 (IDH1/2) mutations in the tissue were determined by either minisequencing or Sanger sequencing. Statistical tests Metabolic differences between IDH mutant and IDH wildtype gliomas were assessed by a Mann-Whitney U-test. A Kruskal-Wallis test followed by a Tukey-Kramer test was used to analyze metabolic differences between IDH and TERTp mutational molecular subsets of gliomas. A Spearman rank correlation coefficient was used to assess the correlations of metabolite intensities with the Ki-67 index. Furthermore, machine learning was employed to classify the IDH and TERTp mutational status of gliomas, and the accuracy, sensitivity, and specificity values were estimated. Results Short-TE 1 H-MRS classified the presence of an IDH mutation with 88.39% accuracy, 76.92% sensitivity, and 94.52% specificity, and a TERTp mutation within primary IDH wildtype gliomas with 92.59% accuracy, 83.33% sensitivity, and 95.24% specificity. Data conclusion Short-TE 1 H-MRS could be used to identify molecular subsets of hemispheric diffuse gliomas corresponding to IDH and TERTp mutations. Level of evidence 3 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;51:1799-1809.

Thyroid cancer (TC) is a very common malignancy worldwide. Chief among the innovative molecular drug targets for TC are epigenetic modifications. Increased telomerase activity in cancer ce...

BackgroundIVSII-74 T > G is one of the most frequently identified polymorphic sites on the β-globin gene. In our report, we present three cases with low mean corpuscular volume (MCV) value in three and high red blood cell (RBC) value in two of the cases. The objective of this study was to further analyse the reason for condition of three patients, who were referred for the investigation of persistent anemia.Materials and MethodsFollowing the HPLC analyses of Hb migration pattern, direct nucleotide sequencing of α- and β-globin genes was performed for all cases.ResultsThe common finding was the homozygosity for the intronic change, IVSII-74 T > G.ConclusionIn the intersection point of the variations on our patients, we claim a homozygous change at position 74 on the intron II of the β-globin gene alone may be sufficient to cause a β-thalassemia carrier phenotype.

AIM: To identify the copy number variations that are specific to myxopapillary ependymomas (MPEs) of the cauda equina. MATERIAL and METHODS: The patient cohort included five patients who underwent resection of histologically confirmed MPEs. Tumor samples collected during surgery and stored in liquid nitrogen as well as corresponding blood samples collected were analyzed. Genomic DNA from the venous blood and tumor samples was obtained using standard techniques and hybridized to a Cytoscan 750K Array in accordance with the manufacturer's introductions. RESULTS: As a novel finding, amplification on chromosome 14q32.33 was detected in all tumor and blood samples, except one tumor sample. All tumor tissues also showed amplification on chromosomes 5, 7, 9, and 16. CONCLUSION: Although further studies with larger cohorts are required to identify genes involved in MPE tumorigenesis and to validate our results, these findings provide a basis for advanced molecular biological and genetic studies of MPEs.

Telomeres, and telomere length in particular, have broad significance for genome biology and thus are prime research targets for complex diseases such as cancers. In this context, BRCA1 and BRCA2 gene mutations have been implicated in relationship to telomere length, and breast cancer susceptibility. Yet, the linkages among human genetic variation and telomere length in persons with high hereditary cancer risk are inadequately mapped. We report here original findings in 113 unrelated women at high hereditary risk for breast cancer, who were characterized for the BRCA1 and BRCA2 mutations using next-generation sequencing. Thirty-one BRCA2 and 21 BRCA1 mutations were identified in 47 subjects (41.6%). The women with a mutation in BRCA1 and/or BRCA2 genes had, on average, 12% shorter telomere compared to women with no BRCA1 or BRCA2 mutation ( p = 0.0139). Moreover, the association between telomere length and BRCA mutation status held up upon stratified analysis in those with or without a breast cancer diagnosis. We also indentified two rare mutations, c.536_537insT and c.10078A>G, and a novel mutation c.8680C>G in BRCA2 that was studied further by homology modeling of the DNA binding tower domain of BRCA2 and the structure of the protein. These data collectively lend evidence to the idea that BRCA1 and BRCA2 mutations play a role in telomere length in women at high hereditary risk for breast cancer. Further clinical and diagnostics discovery research on BRCA1 and BRCA2 variation, telomere length, and breast cancer mechanistic linkages are called for in larger study samples.

Objective Pediatric glial tumors comprise wide range pathologies which may mimic histomorphological features of each other's but generally have very diverse disease course. WHO Classification of Tumors of Central Nervous System (2016 and 2021) points to the necessity of investigating several molecular alterations for integrated pathological diagnosis of childhood CNS tumors. This makes customized next-generation sequencing (NGS) a powerful tool for the diagnosis of childhood CNS tumors. Methodology Acibadem Molecular Pathology Brain Tumor NGS Panel was designed according to targeted deep RNA and DNA sequencing. RNA and DNA were isolated from paraffin blocks containing more than 50% tumor in 45 cases with childhood CNS tumors. Miniseq Sequencing System, Illumina and Archer Analysis Ver 6.0.3.2 platforms were used. Fusions (translocations), mutations, and DNA copy number changes in 81 genes were screened for the most common molecular alterations in CNS tumors. Results Fourty-five childhood CNS tumors were evaluated with NGS results. Among these there were 19 pilocytic astrocytomas, 1 case of high grade astrocytoma with piloid features, 4 diffuse leptomeningeal glioneuronal tumors, 1 pleomorphic xanthoastrocytoma, 4 pediatric diffuse glial tumors, 1 infantile hemispheric astrocytoma, 1 astroblastoma, 12 diffuse midline glioma. Sixteen of these tumors were able to be diagnosed based on these molecular findings. Thirty-four cases received targeted therapies. Conclusion The customized NGS panel, as a single molecular workflow is very helpful and supportive in diagnosis for CNS childhood tumors. Since the number of driver mutations are few in childhood tumors, detection of the driver molecular alteration is guiding the medical treatment startegy in terms of targeted regimens.

Background: Jervell and Lange-Nielsen syndrome (JLNS) isa recessive model of long QT syndrome which might also be related to possible hearing loss. Although the syndrome has been demonstrated to be originated from homozygous or compound heterozygous mutations in either the KCNQ1 or KCNE1 genes, additional mutations in other genetic loci should be considered, particularly in malignant course patients. Case presentations: Three patients were admitted into hospital due to recurrent seizures/syncope, intrauterine and postnatal bradycardia respectively; moreover all three patients had congenital sensorineural hearing-loss. Their electrocardiograms showed markedly prolonged QT interval. Implantable defibrillator was implanted and left cardiac sympathetic denervation was performed due to the progressive disease in case 1. She had countless ventricular fibrillation and appropriate shock while using an implantable defibrillator. The DNA sequencing analysis of the KCNQ1 gene disclosed a homozygous c.728G > A (p.Arg243His) missense mutation in case1. Further targeted next generation sequencing of cardiac panel comprising 68 gene revealed a heterozygous c.1346 T > G (p.Ile449Arg) variant in RYR2 gene and a heterozygous c.809G > A (p.Cys270Tyr) variant in NKX2-5 gene in the same patient. Additional gene alterations in RYR2 and NKX2-5 genes were thought to be responsible for progressive and malignant course of the disease. As a result of DNA sequencing analysis of KCNQ1 and KCNE1 genes, a compound heterozygosity for two mutations had been detected in KCNQ1 gene in case 2: a maternally derived c.477 + 1G > A splice site mutation and a paternally derived c.520C > T (p.Arg174Cys) missense mutation. Sanger sequencing of KCNQ1 and KCNE1 genes displayed a homozygous c.1097G > A (p.Arg366Gln) mutation in KCNQ1 gene in case 3. beta-blocker therapy was initiated to all the index subjects. Conclusions: Three families of JLNS who presented with long QT and deafness and who carry homozygous, or compound heterozygous mutation in KCNQ1 gene were presented in this report. It was emphasized that broad targeted cardiac panels may be useful to predict the outcome especially in patients with unexplained phenotype-genotype correlation. Clinical presentations and molecular findings will be discussed further to clarify the phenotype genotype associations., Ministry of Science, Industry and Technology

Telomerase reverse transcriptase promoter (TERTp) mutations in the absence of IDH mutations (TERTp-only) are recently proposed as a characteristic of glioblastoma regardless of the morphological grade. This study aims to analyze metabolic profiles of TERTp-only gliomas using proton magnetic resonance spectroscopy (1H-MRS) and evaluate the effect of metabolite concentrations on progression-free survival (PFS) and overall survival (OS). The patient cohort consisted of 56 TERTp-only gliomas (35M/21F, mean age: 58±10.37 years, 44 glioblastomas (GBM), and 12 lower-grade gliomas with TERTp-mutation but no IDH-mutations). All patients underwent preoperative diagnostic 1H-MRS using a 3T MR scanner with a 32-channel head coil. 1H-MRS was obtained from a manually placed region of interest with no necrosis, edema, and hemorrhage, using a Point Resolved Spectroscopy (PRESS) sequence (TR/TE=2000/30 ms, 1024 points). LCModel spectral fitting program was used for quantification of MR spectroscopic peak concentrations of 17 metabolites. The patients were divided into two groups using median values of the metabolite intensities, and Kaplan-Meier survival analysis followed by a log-rank test was used to determine the effects of metabolite concentrations on OS and PFS. Median PFS and OS of TERTp-only gliomas were 11 and 17 months, respectively. TERTp-only LGG patients had longer OS and PFS than TERTp-only GBM patients (p=0.022 for OS and p=0.018 for PFS). Significantly shorter OS and PFS were identified in TERTp-only gliomas, who had higher GSH/tCr (p=0.011 for OS and p=0.004 for PFS) and higher Lac/tCr (p=0.014 for OS and p=0.012 for PFS). Lactate is a marker of necrosis and a sign of malignancy. On the other hand, both tCr and GSH were lower, which resulted in higher GSH/tCr, in TERTp-only GBM. The results of this study indicate that high Lac/tCr and GSH/tCr might be indicators of poor prognosis in TERTp-only gliomas. This study has been supported by TUBITAK 1003 grant 216S432.

IDH mutation, a key factor in predicting glioma prognosis, alters the levels of some metabolites in brain, including 2-hydroxyglutarate (2HG), glutamine (Gln), and glutathione (GSH). While proton MR spectroscopy (1H-MRS) enables in-vivo detection of these metabolites, liquid chromatography-mass spectrometry (LC-MS/MS) is a sensitive in-vitro method to measure absolute metabolite concentrations. This study aims to examine the correlation of metabolic concentrations measured using 1H-MRS and LC-MS/MS in gliomas, and to detect IDH mutation with machine learning based on 1H-MRS and LC-MS/MS metabolic intensities. The patient cohort included 178 glioma patients (111M/67F, mean age:44.09±13.95 years, 100 IDH-mut, 78 IDH-wt). The patients were scanned pre-surgery by a 3T MR scanner with a 32-channel head coil. 1H-MRS was obtained from a manually placed region of interest with no necrosis, edema, and hemorrhage, using a Point Resolved Spectroscopy (PRESS) sequence (TR/TE=2000/30ms). LCModel software was used for quantification of eighteen metabolites of 1H-MRS data. Metabolite concentrations including creatine (Cr), choline (Cho), Gln, glutamate (Glu), gamma-aminobutyric acid (GABA), N-acetyl aspartate (NAA), myo-inositol (mIns), 2HG, and lactate (Lac) were also determined with LC-MS/MS for surgical specimen of the same patients. Spearman correlation coefficients were calculated between the metabolite concentrations measured with 1H-MRS and LC-MS/MS. Additionally, machine-learning algorithms were used to detect IDH mutation in gliomas based on metabolite concentrations obtained with 1H-MRS and LC-MS/MS. Consequently, there were statistically significant correlations between 1H-MRS and LC-MS/MS results for 2HG (p=0.036), Cr (p=0.009), mIns (p

Contains fulltext : 172088.pdf (Publisher’s version ) (Open Access) With around 500 cases published worldwide, pulmonary alveolar microlithiasis is a rare disorder with an autosomal recessive pattern of inheritance. We show for the first time that homozygous deletions encompassing the entire SCL34A2 can be associated with this rare genetic pulmonary disease.

PubMed: 30058754 We present three siblings afflicted with a disease characterized by cerebellar ataxia, cerebellar atrophy, pyramidal tract damage with increased lower limb tendon reflexes, and onset of 31 to 57 years, which is not typical for a known disease. In a region of shared homozygosity in patients, exome sequencing revealed novel homozygous c.*240T > C variant in the 3?UTR of STUB1, the gene responsible for autosomal recessive spinocerebellar ataxia 16 (SCAR16). In other genes, such an alteration of the evolutionarily highly conserved polyadenylation signal from AATAAA to AACAAA is known to highly impair polyadenylation. In contrast, RNA sequencing and quantification revealed that neither polyadenylation nor stability of STUB1 mRNA is affected. In silico analysis predicted that the secondary structure of the mRNA is altered. We propose that this change underlies the extremely low amounts of the encoded protein in patient leukocytes. © 2018 Wiley Periodicals, Inc. Türkiye Bilimsel ve Teknolojik Araştirma Kurumu, TÜBITAK: 114Z829 Türkiye Bilimsel ve Teknolojik Araştirma Kurumu, TÜBITAK Sehime G. Temel, Department of Medical Genetics, Department of Histology and Embryology, Faculty of Medicine, Uludag? University, Gorukle Campus, 16059 Nilufer, Bursa, Turkey Email: sehimegtemel@hotmail.com Aslıhan Tolun, Department of Molecular Biology andGenetics,Bog?aziçiUniversity,Istanbul, Turkey. Email: tolun@boun.edu.tr Funding Information This study was supported by the Scientific and Technological Research Council of Turkey (TÜBITAK) Grant 114Z829.

Background: Pathological inflammatory syndromes of unknown etiology are commonly observed in ataxia telangiectasia (AT) and Artemis deficiency. Similar inflammatory manifestations also exist in patients with STING-associated vasculopathy in infancy (SAVI). Objective: We sought to test the hypothesis that the inflammation-associated manifestations observed in patients with AT and Artemis deficiency stem from increased type I IFN signature leading to neutrophil-mediated pathological damage. Methods: Cytokine/protein signatures were determined by ELISA, cytometric bead array, or quantitative PCR. Stat1 phosphorylation levels were determined by flow cytometry. DNA species accumulating in the cytosol of patients' cells were quantified microscopically and flow cytometrically. Propensity of isolated polymorhonuclear granulocytes to form neutrophil extracellular traps (NETs) was determined using fluorescence microscopy and picogreen assay. Neutrophil reactive oxygen species levels and mitochondrial stress were assayed using fluorogenic probes, microscopy, and flow cytometry. Results: Type I and III IFN signatures were elevated in plasma and peripheral blood cells of patients with AT, Artemis deficiency, and SAVI. Chronic IFN production stemmed from the accumulation of DNA in the cytoplasm of AT and Artemis-deficient cells. Neutrophils isolated from patients spontaneously produced NETs and displayed indicators of oxidative and mitochondrial stress, supportive of their NETotic tendencies. A similar phenomenon was also observed in neutrophils from healthy controls exposed to patient plasma samples or exogeneous IFN-α. Conclusions: Type I IFN-mediated neutrophil activation and NET formation may contribute to inflammatory manifestations observed in patients with AT, Artemis deficiency, and SAVI. Thus, neutrophils represent a promising target to manage inflammatory syndromes in diseases with active type I IFN signature. © 2017 American Academy of Allergy, Asthma & Immunology.

WOS: 000358382400025, PubMed ID: 26005079, Meningomyelocele is one of the most common and socioeconomically, psychologically, and physically debilitating neurodevelopmental diseases. A few chromosomal locus and genes have been identified as responsible for the disease; however, clear evidence still needs to be produced. This study aimed to show evidence of a strong genetic linkage in a novel chromosomal locus in a family with this neural tube defect. We identified a neural tube defect family in eastern Turkey, where two of six offspring had operations due to thoracolumbar meningomyelocele. The parents were of a consanguineous marriage. We collected venous blood from six offspring of the family. Whole genome linkage analysis was performed in all offspring. A theoretical maximum logarithm of an odds score of 3.16 was identified on chromosome 9q21.12-21.31. This result shows a strong genetic linkage to this locus. Our results identified a novel chromosomal locus related to meningomyelocele and provide a base for further investigations toward the discovery of a new causative gene.

Behçet's disease (BD) is a chronic inflammatory autoimmune disease. Although raised levels of proinflammatory cytokines in BD have been reported, the pathogenesis is still unknown. The aim of this study was to investigate the association of NFKB1 and NFKBIA polymorphisms and their single and combined analysis effects on susceptibility of BD in Turkish population. We analysed the distribution of NFKB1 -94 ins/del ATTG (rs28362491) and NFKBIA 3' UTR A→G (rs696) polymorphisms using PCR-RFLP method in 89 patients with BD and 190 controls in this population. Statistical analysis of the results was performed by calculating OR, and 95% CI via χ(2) test and using Bonferroni correction. According to the significant results of both single and combined genotype analysis, the frequencies of ins/ins genotype and ins allele of rs28362491 were significantly higher in patients with BD (Pc = 0.003, 0.004, respectively). Also, higher frequencies of the rs696 variant containing AA genotype was found in patients with BD (Pc = 0.0033), whereas no statistical significant differences in distribution of the alleles of rs696 polymorphism in patients and controls. In addition, according to the combined genotype analysis, the wild type of both rs28362491 and rs696 polymorphisms (ins/ins/AA genotype) was also significantly higher in BD cases (Pc = 0.044). Our findings prove that both single and combined genotype analysis of rs28362491 and rs696 polymorphisms indicate that the wild genotypes of both two SNPs (ins/ins and AA genotypes) and ins/ins/AA combined genotype are strongly associated with enhanced risk of BD in a Turkish population.

Objectives/Hypothesis To achieve injectable tissue-engineered cartilage using a commercially available fibrin sealant, and to determine the most suitable fibrin glue concentration, cartilage source, and cultured chondrocyte concentration. Study Design Animal research. Methods A total of 28 immuncompetent New Zealand white rabbits were divided into four groups. The cultured chondrocytes from different anatomical sources carried in fibrin glue with and without aprotinin in different concentrations of fibrinogen and thrombin (Tisseell), were injected into forehead and interocular regions of the rabbits. The new tissue formation was harvested at 8 weeks and analyzed through gross and histological analysis. Results The new tissue formations were found in round, elliptical, and flat forms. The mean value of Tisseell and cell suspension was 0.8 cc in all of the rabbits' injection regions, but the mean volume of the samples in which immature cartilage matrix and mature cartilage was 0.1 cc. In the 20 of the 55 injection regions of rabbits (36, 36%), mature and/or immature cartilage formation were observed. We observed inflammatory reactions, abscess formation, and foreign body reactions around the new cartilage tissue of tissue-engineered cartilage. The comparison of results using different cartilage sources, chondrocyte concentrations, or different fibrin glue concentrations did not show any significant difference. Conclusions We observed that changing the concentrations of ingredients of commercially available fibrin glue, the source of the cartilage, or the cultured chondrocyte concentration did not have significant effect on neocartilage formation. Level of Evidence N/A. Laryngoscope, 123:2986–2992, 2013

Meningiomas are one of the most common tumours to affect the central nervous system. Genetic mutations are important in meningeal tumourigenesis, progression and prognosis. In this study, we aimed to examine the effect of 1p/19q deletion on the diagnosis and prognosis of meningioma subtypes using the fluorescence in situ hybridization (FISH) method.Twenty-four patients with meningioma were retrospectively studied. Tumour samples were obtained from 10 typical, 11 atypical and three anaplastic malignant meningiomas. The most representative tumour sections were screened for 1p/19q deletion using the FISH method.Of the 24 patients, eight were women (33.3%) and 16 (66.7%) were men. The mean age was 56.6 years. The higher-grade meningioma was usually seen in males and had a higher rate of deletion on 1p (p = 0.001). There was a statistically significant difference between the grades and the rate of deletion on 19q (p = 0.042) and between the grades and the rates of polysomy, monosomy and amplification on 19q (p = 0.002; p = 0.001; p = 0.002, respectively). There was no statistical difference between 1p/19q codeletion and the grades of meningioma (p 0.05). We detected higher level of Ki-67 in the condition of codeletion but did not find a statistical difference (p = 0.0553).Deletion on 1p, as well as deletion, polysomy, monosomy and amplification on 19q, are detected more frequently in high grade meningiomas. This amplification is most likely due to the amplification of oncogenes.

Background/aim: Previously we showed that Fms-like tyrosine kinase (FLT3) changes its cellular localization upon partial hepatectomy, suggesting a role in liver regeneration. FLT3 was also shown to play an important function in cellular proliferation and activation of PI3K and Ras. Thus, we aimed to investigate the role of FLT3 in hepatocellular tumorigenesis utilizing in vitro and in vivo models. Materials and methods: We used Snu398 cells that express FLT3. We investigated these cells' in vitro proliferation and invasion abilities by treatment with the FLT3 inhibitor K-252a or by knocking-down with FLT3 shRNA,. Furthermore, the effect of blocking FLT3 activity and expression during in vivo tumorigenesis was assessed with xenograft models. Results: After K-252a treatment or stable knock-down, these cells' proliferation and migration abilities were highly diminished in vitro. In addition, significant diminution in tumorigenicity of Snu398 cells was also obtained in vivo. When FLT3 knocked-down Snu398 cells were injected into nude mice, we did not detect αSMA expression in these tumors, suggesting a role for FLT3 in in vivo invasiveness. Conclusion: Our data provided evidence that FLT3 has a crucial role both in hepatocarcinogenesis and its invasiveness. Therefore, targeting FLT3 and/or its activity may be a promising tool for combating hepatocellular carcinomas.

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MiRNAs and NFKB1 are well-known immune response and inflammation regulators. MiRNA gene polymorphisms may affect miRNA biogenesis and function and, may thus, lead to changes in the expression of hundreds of genes such as NFKB1. The aim of this study was to investigate the association of Behcet's disease (BD) with NFKB1 rs28362491, pre-miRNA-146a rs2910164, and pre-miRNA-499 rs3746444 polymorphisms, as well as the analysis of their single and combined effects on its susceptibility in a Turkish population. These polymorphisms were analyzed by using the polymerase chain reaction-restriction fragment length polymorphism method in 100 BD patients and 145 healthy control subjects. The results were analyzed statistically using Pearson chi-square (χ(2)) test and Fisher's exact test (two sided). According to genotype analysis, the frequencies of ins/ins genotype and ins allele of rs28362491 were considerably higher in BD patients. Also, miRNA-499 rs3746444 homozygous (TT) genotypes exibited a significantly higher risk in patients with BD (odds ratios [OR]=3.0, 95% confidence intervals [95% CI]=1.284-7.007, p=0.017). Moreover, the frequency of T allele of rs3746444 was a risk factor for BD (OR=1.562, 95% CI=1.087-2.24, p=0.015). In addition, significant differences were found between the groups concerning miRNA-146a rs2910164 polymorphism. Homozygous CC genotype and C allele of rs2910164 polymorphism were found to be protective factors against BD. The results of the combined genotype analysis showed no notable differences between the multiple comparisons of rs28362491-rs2910164 and of rs28362491-rs3746444 in patients and control groups. Our data demonstrate that homozygous CC genotype and C allele of rs2910164 polymorphism are protective factors against BD, but rs3746444 and rs28362491 polymorphisms in miRNA-499 and in NFKB1 promoter are involved in the genetic susceptibility of BD. In addition, TT and ins/ins genotypes may influence certain proinflammatory cytokines and, may thus, play a role in the pathogenesis of BD.

We report an association between a new causative gene and spastic paraplegia, which is a genetically heterogeneous disorder. Clinical phenotyping of one consanguineous family followed by combined homozygosity mapping and whole-exome sequencing analysis. Three patients from the same family shared common features of progressive complicated spastic paraplegia. They shared a single homozygous stretch area on chromosome 6. Whole-exome sequencing revealed a homozygous mutation (c.853\_871del19) in the gene coding the kinesin light chain 4 protein (KLC4). Meanwhile, the unaffected parents and two siblings were heterozygous and one sibling was homozygous wild type. The 19 bp deletion in exon 6 generates a stop codon and thus a truncated messenger RNA and protein. The association of a KLC4 mutation with spastic paraplegia identifies a new locus for the disease.

PTPRD (protein tyrosine phosphatase, receptor type, D) is a tumor suppressor gene, frequently inactivated through deletions or epigenetic mechanisms in several cancers with importance for global health. In this study, we provide new and functionally integrated evidence on genetic and epigenetic alterations of PTPRD gene in hepatocellular carcinomas (HCCs). Importantly, HCC is the sixth most common malignancy and the third most common cause of cancer-related mortality worldwide. We used a high throughput single nucleotide polymorphism (SNP) microarray assay (Affymetrix, 10K2.0 Assay) covering the whole genome to screen an extensive panel of HCC cell lines (N=14 in total) to detect DNA copy number changes. PTPRD expression was determined in human HCCs by Q-RT-PCR and immunohistochemistry. Promoter hypermethylation was assessed by combined bisulfite restriction analysis (COBRA). DNA methyl transferase inhibitor 5-azacytidine (5-AzaC) and/or histone deacetylase inhibitor Trichostain A (TSA) were used to restore the expression. We identified homozygous deletions in Mahlavu and SNU475 cells, in the 5′UTR and coding regions, respectively. PTPRD mRNA expression was downregulated in 78.5% of cell lines and 82.6% of primary HCCs. PTPRD protein expression was also found to be lost or reduced in HCC tumor tissues. We found promoter hypermethylation in 22.2% of the paired HCC samples and restored PTPRD expression by 5-AzaC and/or TSA treatments. In conclusion, PTPRD is homozygously deleted and epigenetically downregulated in HCCs. We hypothesize PTPRD as a tumor suppressor candidate and potential cancer biomarker in human HCCs. This hypothesis is consistent with compelling evidences in other organ systems, as discussed in this article. Further functional assays in larger samples may ascertain the contribution of PTPRD to hepatocarcinogenesis in greater detail, not to forget its broader importance for diagnostic medicine and the emerging field of personalized medicine in oncology. © Copyright 2015, Mary Ann Liebert, Inc. 2015.

A 38‐year‐old female with chronic myeloid leukemia underwent an allogeneic bone marrow transplantation from her full‐matched brother. Eleven months later, she readmitted with an acute leukemia that was shown to be of donor origin. The patient never achieved a remission even after chemotherapies with cytarabine and mitoxantrone, donor lymphocyte infusion, and second allogeneic peripheral blood stem cell transplantation. Donor cell leukemia (DCL) is sometimes misdiagnosed as relapse by clinicians and the real incidence may be higher than expected. Cytogenetic and molecular techniques may be helpful to clarify the issue of the leukemia. The current case is another case of DCL reported in the literature after an allogeneic transplant for a kind of leukemia. Am. J. Hematol. 81:370–373, 2006

MicroRNA (miRNA) deregulation is associated with various cancers. Among an expanding list of cancer-related miRNAs, deregulation of miR-125b has been well documented in many cancers including breast. Based on current knowledge, miR-125b is considered to be a tumor suppressor in breast cancers. While important messenger RNA (mRNA) targets have been defined for miR-125b, here, we aimed to further investigate direct/indirect consequences of miR-125b expression in breast cancer cells by using a transcriptome approach. Upon miR-125b expression, a total of 138 cancer-related genes were found to be differentially expressed in breast cancer cells. While only a few of these were predicted to be direct mRNA targets, majority of the gene expression changes were potentially downstream and indirect effects of miR-125b expression. Among these, activated leukocyte antigen molecule (ALCAM) mRNA and protein levels were found to be highly significantly increased upon miR-125b expression. Given the tumor suppressor role of miR-125b in our model system, upon silencing of ALCAM expression, cell proliferation rate re-increased in miR-125b-expressing cells. While ALCAM's possible context-dependent roles are not clear in breast cancer, a diverse expression pattern of ALCAM mRNA was detected in a panel of breast cancer patient samples. Differentially expressed/regulated cancer-related genes upon miR-125b expression along with the significant increase of ALCAM are of future interest to understand how deregulated expression of miR-125b may have a tumor suppressor role in breast and other cancers.

To evaluate the prevalence of coexisting anal human papillomavirus (HPV) infection and concordance of HPV types in women with cervical HPV infection and to investigate the possible predictors for anal HPV infection. Study group was composed of women referred with documented cervical HPV infection. All patients had undergone anal HPV DNA testing. One hundred and six patients presenting with cervical HPV infection were eligible for the study. Overall, 24 and 20 distinct HPV genotypes were detected from cervical and anal specimens, respectively. We observed a considerably high prevalence (51.9 %) of coexisting anal HPV infection in our study group. A majority of the women who were found to have anal HPV infection were infected with oncogenic or probable oncogenic types (64.6 %). There were 20.0 and 58.3 % rate of total and partial concordance between the two sites, respectively. We found that no demographic parameter but history of anal intercourse was related with the risk of anal HPV infection. Women with cervical HPV infection have a considerable risk for coexisting anal HPV infection. Concordance of HPV types infecting the cervix and anal canal is relatively high. There is no strong predictor for anal HPV infection in this population.

Muscle Hemangiomatosis Presenting as a Severe Feature in a Patient with the Pten Mutation: Expanding the Phenotype of Vascular Malformations in Bannayan-Riley-ruvalcaba SyndromeBannayan-Riley-Ruvalcaba syndrome (BRRS) is a rare autosomal, dominantly-inherited, hamartoma syndrome with distinct phenotypic features. Mutations in the PTEN gene have been identified in PTEN hamartoma tumor syndromes. Our aim was to determine the correlation of phenotype-genotype relationships in a BRRS case. We have evaluated a PTEN mutation in a patient with vascular anomalies and the phenotypic findings of BRRS. We described an 8-year-old girl with the clinical features of BRRS, specifically with vascular anomalies. The mutation in the PTEN gene was identified by DNA sequencing. In our patient, we defined a de novo nonsense R335X (c.1003 C>T) mutation in exon 8, which results in a premature termination codon. Due to vascular anomalies and hemangioma, the patient's left leg was amputated 1 year after the hemangioma diagnosis. Bannayan - Riley - Ruvalcaba syndrome patients with macrocephaly and vascular anomalies should be considered for PTEN mutation analysis and special medical care.

We studied 80 hepatocellular carcinomas from three continents for p53 gene (TP53) mutations and hepatitis B virus (HBV) sequences. p53 mutations were frequent in tumors from Mozambique but not in tumors from South Africa, China, and Germany. Independent of geographic origin, most tumors were positive for HBV sequences. X gene coding sequences of HBV were detected in 78% of tumors, whereas viral sequences in the surface antigen- and core antigen-encoding regions were present in less than 45% of tumors. These observations indicate that hepatocellular carcinomas are genetically heterogeneous. Mozambican-type of hepatocellular carcinomas are characterized by a high incidence of p53 mutations related to aflatoxins. In other tumors, the rarity of p53 mutations combined with the frequent presence of viral X gene coding sequences suggests a possible interference of HBV with the wild-type p53 function.

Background Smad interacting protein-1 is a transcription factor that is implicated in transforming growth factor-β/bone morphogenetic protein signaling and a repressor of E-cadherin and human telomerase reverse transcriptase. It is also involved in epithelial-mesenchymal transition and tumorigenesis. However, genetic and epigenetic alterations of SIP1 have not been fully elucidated in cancers. In this study, we investigated mutations and promoter hypermethylation of the SIP1 gene in human hepatocellular carcinomas. Methods SIP1 expression was analyzed in HCC cell lines and primary tumors in comparison to normal and non-tumor liver tissues by using semi-quantitative RT-PCR, quantitative real-time RT-PCR and immunohistochemistry. Mutation and deletion screening of the SIP1 gene were performed by direct sequencing in HCC-derived cells. Restoration of SIP1 expression was sought by treating HCC cell lines with the DNA methyl transferase inhibitor, 5-AzaC, and the histone deacetylase inhibitor, TSA. SIP1 promoter methylation was analyzed by the combined bisulfite restriction analysis assay in in silico-predicted putative promoter and CpG island regions. Results We found that the expression of SIP1 was completely lost or reduced in five of 14 (36%) HCC cell lines and 17 of 23 (74%) primary HCC tumors. Immunohistochemical analysis confirmed that SIP1 mRNA downregulation was associated with decreased expression of the SIP1 protein in HCC tissues (82.8%). No somatic mutation was observed in SIP1 exons in any of the 14 HCC cell lines. Combined treatment with DNA methyl transferase and histone deacetylase inhibitors synergistically restored SIP1 expression in SIP1-negative cell lines. Analysis of three putative gene regulatory regions revealed tumor-specific methylation in more than half of the HCC cases. Conclusions Epigenetic mechanisms contribute significantly to the downregulation of SIP1 expression in HCC. This finding adds a new level of complexity to the role of SIP1 in hepatocarcinogenesis.

Cataloged from PDF version of article. Loss of function of the p53 protein, which may occur through a range of molecular events, is critical in hepatocellular carcinoma (HCC) evolution. MDM2, an oncogene, acts as a major regulator of the p53 protein. A polymorphism in the MDM2 promoter, SNP309 (T/G), has been shown to alter protein expression and may thus play a role in carcinogenesis. MDM2 SNP309 is also associated with HCC. However, the role of SNP309 in hepatocarcinogenesis with respect to TP53 mutations is unknown. In this study, we investigated the distribution of the MDM2 SNP309 genotype and somatic TP53 (the p53 tumor suppressor gene) mutations in 99 human HCC samples from Africa, Europe, China and Japan. Samples exhibited striking geographical differences in their distribution of SNP309 genotypes. The frequency and spectrum of p53 mutations also varied geographically; TP53 mutations were frequent in Africa, where the SNP309 T/T genotype predominated but were rare in Europe and Japan, where the SNP309 G allele was present more frequently. TP53 mutations were detected in 18% (4/22) of SNP309 T/G and G/G and 82% (18/22) of SNP309 T/T genotype holders; this difference was statistically highly significant (P-value = 0.0006). Our results indicated that the presence of the SNP309 G allele is inversely associated with the presence of somatic TP53 mutations because they only coincided in 4% of HCC cases. This finding suggests that the SNP309 G allele may functionally replace p53 mutations, and in addition to known etiological factors, may be partly responsible for differential HCC prevalence. (C) 2009 Elsevier B.V. All rights reserved.

Choroid plexus papilloma (CPP) is a rare, benign epithelial brain tumor of the nervous system seen particularly in infants. Familial cases are extremely uncommon. Some other form of malignant tumors was noted in the relatives of patients with CPPs, and some genetic defects regarding this coincidence were reported in the literature. These neoplasms are occasionally bilateral and hydrocephalus is an associated sign in most of the cases. We report three lateral ventricle CPPs in two siblings, at the age of 7 month and 2 years respectively. All tumors were resected with parietotemporal craniotomy and a superior temporal sulcus approach to the lateral ventricle. To avoid a concomitant need of ventriculoperitoneal shunt insertion, external ventricular drainage was inserted for a week in the postoperative period relieving symptoms of hydrocephalus. Search for a hereditary defect in the p53 gene of the second infant (7 months old) revealed no mutation. Postoperative courses were uneventful and the patients were followed for three years without any recurrence. Bilateral CPPS are rare and unusual in two siblings. A genetic predisposition such as the p53 mutation should be investigated in bilateral CPPs in particular.

Various regions of amplification or loss are observed in breast tumors as a manifestation of genomic instability. To date, numerous oncogenes or tumor suppressors on some of these regions have been characterized. An increasing body of evidence suggests that such regions also harbor microRNA genes with crucial regulatory roles in cellular processes and disease mechanisms, including cancer. Here, we investigated 35 microRNAs localized to common genomic gain and/or loss regions in breast cancers. To examine amplification or loss of these microRNAs as a result of genomic instability, we performed semiquantitative duplex polymerase chain reaction in 20 breast cancer cell lines, 2 immortalized mammary cell lines, and 2 normal DNA controls. A comprehensive DNA fold number change data for 35 microRNA genes on chromosomal gain/loss regions are presented in breast cancer cells. A 23% (8/35) of the investigated microRNAs showed significant fold number increases (greater than fourfold) compared to GAPDH in one or more of the breast cell lines. Although no homozygous deletions were detected, fold number decreases indicating potential loss regions were observed for 26% (9/35) of the investigated microRNAs. Such fold number changes may point out some of these microRNAs as potential targets of the genomic instability regions as oncogene and tumor suppressor candidates. © 2009 Elsevier Inc. All rights reserved.

YAS, Ozlem BUYUKTANIR/0000-0002-7641-7350 WOS: 000255990700014 PubMed: 18248920 Mycoplasma gallisepticum is the primary agent of chronic respiratory disease causing important economic losses in the poultry industry. Serological monitoring is essential to maintain mycoplasma-free breeder flocks and often complicated by the cross-reactions between different mycoplasma species. To overcome serological cross-reactions, a large fragment of the M. gallisepticum PvpA cytadhesin, species-specific surface-exposed protein, was produced in E. coli as a recombinant protein (rPvpA336) and used as a potential diagnostic antigen. The rPvpA336 protein possesses 336 mycoptasma-specific amino acids with relative molecular weight of 44 kDa. A deletion region of 37 amino acids was identified when compared to the wild-type PvpA protein. Immunoreactivity of the rPvpA336 protein has been demonstrated by Western blot analysis with M. gallisepticum-positive and -negative chicken sera. Furthermore, an enzymatic rapid immunofiltration assay (ERIFA) prototype based on the rPvpA336 protein has been developed and its species-specific detection capability has been demonstrated by using M. gallisepticum and/or M. synoviae-positive and -negative chicken sera. In addition to its species-specificity, the ERIFA prototype presents certain advantages such as rapidity, field-applicability and cost-effectiveness. Therefore, these advantages would make the prototype a species-specific rapid diagnostic tool of choice in the field and limited laboratory conditions for screening M. gallisepticum infections. (C) 2007 Elsevier B.V. All rights reserved.

The Cretaceous-Eocene volcano-sedimentary units of the Zonguldak region of the western Black Sea consist of subalkaline andesite and tuff, and sandstone dominated by smectite, kaolinite, accessory chlorite, illite, mordenite, and analcime associated with feldspar, quartz, opal-CT, amphibole, and calcite. Kaolinization, chloritization, sericitization, albitization, Fe-Ti-oxidation, and the presence of zeolite, epidote, and illite in andesitic rocks and tuffaceous materials developed as a result of the degradation of a glass shards matrix, enclosed feldspar, and clinopyroxene-type phenocrysts, due to alteration processes. The association of feldspar and glass with smectite and kaolinite, and the suborientation of feldspar-edged, subparallel kaolinite plates to fracture axes may exhibit an authigenic smectite or kaolinite. Increased alteration degree upward in which Al, Fe, and Ti are gained, and Si, Na, K, and Ca are depleted, is due to the alteration following possible diagenesis and hydrothermal activities. Micromorphologically, fibrous mordenite in the altered units and the presence of needle-type chrysotile in the residential buildings in which cancer cases lived were detected. In addition, the segregation pattern of cancer susceptibility in the region strongly suggested an environmental effect and a genetic influence on the increased cancer incidence in the region. The most likely diagnosis was Li-Fraumeni syndrome, which is one of the hereditary cancer predisposition syndromes; however, no mutations were observed in the p53 gene, which is the major cause of Li-Fraumeni syndrome. The micromorphology observed in the altered units in which cancer cases were detected may have a role in the expression of an unidentified gene, but does not explain alone the occurrence of cancer as a primary cause in the region. © 2007 Springer-Verlag.

WOS: 000240224100001, Objectives. Behcet's disease (BD) is a systemic vasculitis with recurrent oral and genital ulcers and uveitis. MEFV gene, which is the main factor in familial Mediterranean fever (FMF), is also reported to be a susceptibility gene for BD. The pyrin domain of MEFV gene is a member of death-domain superfamily and has been proposed to regulate inflammatory signaling in myeloid cells. This study was designed to determine if mutations in pyrin domain of MEFV gene are involved in BD. Methods. We analyzed the pyrin domain of MEFV gene in 54 Turkish patients with BD by PCR-analysis and direct sequencing. Results. Neither deletion or insertion mutations nor point mutations in pyrin domain were found in any patient. Conclusion. Although pyrin gene mutations have been reported in patients with BD, pyrin domain is not mutated. However, alterations in other regions of MEFV gene and interaction between pyrin domains are needed to be further investigated. Copyright (c) 2006 Ahmet Dursun et al.

Li-Fraumeni syndrome is a familial cancer syndrome characterized by different tumors and hereditary p53 mutations. Here, a chronic myeloid leukemia-like syndrome case in a Li-Fraumeni syndrome family with del (12) (p12) cytogenetic abnormality was presented. A hereditary p53 mutation (pro309ser) supported the Li-Fraumeni syndrome diagnosis in this family. This syndrome was characterized by the clonal myeloproliferative accumulation in bone marrow and peripheral blood with negative bcr/abl gene rearrangement finding. The etiology of this rare syndrome is still unclear. This is the only chronic myeloid leukemia-like syndrome case reported in a Li-Fraumeni syndrome family. Del (12) (p12) was observed in leukemias except chronic myeloid leukemia-like syndrome. The deletion in chromosome 12pl2 with hereditary p53 mutation should have a critical role in chronic myeloid leukemia-like syndrome etiology in our case. © 2005 Blackwell Publishing Ltd.

WOS: 000227528800010, PubMed: 15903027, Objective: Behcet's disease ( BD) is a rare, chronic, multisystem inflammatory disorder. The prevalence of BD is higher in the Middle Eastern and Mediterranean populations. Another chronic inflammatory disease, familial Mediterranean fever (FMF), is also known to be highly prevalent in these populations. The prevalence of BD is higher in the FMF patient population than in populations known to be rich in BD. Both BD and FMF have some pathophysiological features in common and they result from inappropriate activation of neutrophils. Clinical manifestations of both diseases can mimic each other and the coexistence of both diseases in the same patient has been reported. Given that BD and FMF have similar pathophysiological, epidemiological, and clinical features, we hypothesized that the gene responsible for FMF, MEFV, may also play a role in the pathogenesis of BD. Methods: Forty-two BD patients who had no symptoms and family history for FMF and 66 healthy controls were screened for common MEFV gene mutations (E148Q, M680I, M694V, and V726A). Results: Fifteen patients (36%) displayed MEFV mutations ( nine M694V, five E148Q, and one M680I) and mutation rates were significantly elevated compared to 66 (11%) healthy controls (p=0.0034). Conclusion: The occurrence of frequent MEFV mutations in BD patients suggests that the MEFV gene is involved in the pathogenesis of Behcet's disease.

The limb girdle muscular dystrophies are a heterogeneous group of conditions characterized by proximal muscle weakness and disease onset ranging from infancy to adulthood. We report here eight patients from seven unrelated families affected by a novel and relatively mild form of autosomal recessive limb girdle muscular dystrophy (LGMD2) with onset in the first decade of life and characterized by severe mental retardation but normal brain imaging. Immunocytochemical studies revealed a significant selective reduction of alpha-dystroglycan expression in the muscle biopsies. Linkage analysis excluded known loci for both limb girdle muscular dystrophy and congenital muscular dystrophies in the consanguineous families. We consider that this represents a novel form of muscular dystrophy with associated brain involvement. The biochemical studies suggest that it may belong to the growing number of muscular dystrophies with abnormal expression of alpha-dystroglycan. (C) 2003 Published by Elsevier B.V.

Loss of heterozygosity (LOH) represents the most frequent genetic alteration observed in hepatocellular carcinoma (HCC). Chromosome 16q is of particular interest as it exhibits LOH in 29% of HCC tumors and is frequently lost in breast, prostate, ovarian and gastric carcinomas. We genotyped 157 HCC tumors for 17 microsatellite markers distributed on chromosome 16q and determined a common region of LOH localized between the markers D16S518 and D16S504. By refining the boundaries of two interstitial LOH and two homozygous deletions, the critical region was delimited to 180 kb between D16S3096 and D16S3029. This region is located in intron 8 of the WWOX/FOR gene, but a search for mutations in all coding exons of this gene in 27 HCC tumors and cell lines did not reveal any tumor somatic alterations. Furthermore, by RT-PCR, no abnormal transcripts of this WWOX/FOR gene was detected in nine HCC cell lines. Finally, analysis of the p53 gene mutations with the clinical parameters of all tumors revealed that the two homozygous deletions have occurred in tumors presenting a R249S mutation. Our data revealed a relationship between chromosome 16q homozygous deletions and R249S p53 mutations in tumors where the patient had been exposed to aflatoxin B1 (P=0.002). These results are consistent with a role of aflatoxin B1 in the instability of chromosome 16q at the fragile site FRA16D. However, the nature of the specific gene that is altered during hepatocarcinogenesis remains to be elucidated.

TGF-beta is a negative regulator of liver growth. Smad family of genes, as mediators of TGF-beta pathway, are candidate tumor suppressor genes in hepatocellular carcinoma (HCC). We studied 35 HCC and non-tumour liver tissues for possible mutations in Smad2 and Smad4 genes. Three tumours displayed somatic mutations; two in Smad4 (Asp332Gly and Cys401Arg) and one in Smad2 (Gln407Arg) genes. All three mutations were A:T --> G:C transitions suspected to result from oxidative stress as observed in mitochondrial DNA. These observation demonstrate that TGF-beta pathway is altered in hepatocellular carcinoma.

WOS: 000325205700001, PubMed ID: 24073994, Background: Klippel-Feil syndrome (KFS) is characterized by the developmental failure of the cervical spine and has two dominantly inherited subtypes. Affected individuals who are the children of a consanguineous marriage are extremely rare in the medical literature, but the gene responsible for this recessive trait subtype of KFS has recently been reported. Results: We identified a family with the KFS phenotype in which their parents have a consanguineous marriage. Radiological examinations revealed that they carry fusion defects and numerical abnormalities in the cervical spine, scoliosis, malformations of the cranial base, and Sprengel's deformity. We applied whole genome linkage and whole-exome sequencing analysis to identify the chromosomal locus and gene mutated in this family. Whole genome linkage analysis revealed a significant linkage to chromosome 17q12-q33 with a LOD score of 4.2. Exome sequencing identified the G > A p.Q84X mutation in the MEOX1 gene, which is segregated based on pedigree status. Homozygous MEOX1 mutations have reportedly caused a similar phenotype in knockout mice. Conclusions: Here, we report a truncating mutation in the MEOX1 gene in a KFS family with an autosomal recessive trait. Together with another recently reported study and the knockout mouse model, our results suggest that mutations in MEOX1 cause a recessive KFS phenotype in humans., Cumhuriyet University [T-455, T-496], This work is supported by the Scientific Research Project Fund of Cumhuriyet University under project numbers T-455 and T-496.

Introduction: Genomic instability is a hallmark of ovarian cancer. MicroRNAs (miRNAs) are small RNA molecules that negatively regulate gene expression, and are often dysregulated in cancer. The aim of this study is to determine whether copy number variations (CNV) lead to altered miRNA expression and downstream effects on target gene expression in serous epithelial ovarian cancer (SEOC). Materials and Methods: CN, mRNA and miRNA expression profiling was performed on 4 SEOC (OV167, OV202, OVCAR-3, PE01) and 1 normal (HOSE) cell lines using Affymetrix Cytogenetic 2.7M Arrays, Affymetrix GeneChip Gene 1.0 ST arrays and Exiqon MiRCURY LNA arrays respectively. Chromosomal positioning of miRNAs was performed using Bowtie v 0.12.7 [1]. Results and Discussion: We determined that 60% (361/605) of miRNAs assessed were in regions of CNV in at least 2 cancer cell lines. Of these miRNAs, 32% (115/361) had changes in expression levels that correlated with CNV. One of these, miR-23a, is predicted to target AXL, an oncogenic receptor tyrosine kinase upstream of the PI3K/mTOR signalling pathway. AXL is over-expressed in ovarian cancer, and an inverse relationship was identified between the expression of AXL and miR-23a in 2 of the 4 cell lines. Axl has been previously reported to be over-expressed in 73% of ovarian tumour samples [2]. Transient transfection of miRNA mimics (Ambion) into ovarian cancer cell lines confirmed AXL down regulation after miR-23a addition. Conclusion: We demonstrate that approximately one third of miRNAs that are located in regions of CNV have altered expression which correlates with the chromosomal change. We conclude that genomic instability may contribute to miRNA dysregulation in ovarian cancer.