Nurten Yigit

Nurten Yigit
Ghent University | UGhent · Center for Medical Genetics

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81
Publications
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Publications

Publications (81)
Preprint
Skeletal muscle is an inherently heterogenous tissue comprised primarily of myofibers, which are historically classified into three distinct fiber types in humans: one “slow” (type 1) and two “fast” (type 2A and type 2X), delineated by the expression of myosin heavy chain isoforms (MYHs). However, whether discrete fiber types exist or whether fiber...
Article
Full-text available
The detection of circular RNA molecules (circRNAs) is typically based on short-read RNA sequencing data processed using computational tools. Numerous such tools have been developed, but a systematic comparison with orthogonal validation is missing. Here, we set up a circRNA detection tool benchmarking study, in which 16 tools detected more than 315...
Article
Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Owing to a lack of effective treatments, patients with metastatic disease have a median survival time of 6-12 months. We recently demonstrated that the Survival Associated Mitochondrial Melanoma Specific Oncogenic Non-coding RNA (SAMMSON) is essential for UM cell survi...
Article
Full-text available
Accurate assessment of treatment response and residual disease is indispensable for the evaluation of cancer treatment efficacy. However, performing tissue biopsies for longitudinal follow-up poses a major challenge in the management of solid tumours like neuroblastoma. In the present study, we evaluated whether circulating miRNAs are suitable to m...
Preprint
Full-text available
The detection of circular RNA molecules (circRNAs) is typically based on short-read RNA sequencing data processed by computational detection tools. During the last decade, a plethora of such tools have been developed, but a systematic comparison is missing. Here, we set up a circRNA detection tool benchmarking study, in which 16 tools were used and...
Article
Molecular phenotyping through shallow 3′‐end RNA‐sequencing workflows is increasingly applied in the context of large‐scale chemical or genetic perturbation screens to study disease biology or support drug discovery. While these workflows enable accurate quantification of the most abundant genes, they are less effective for applications that requir...
Article
Full-text available
Long non-coding RNAs (lncRNAs) can exhibit cell-type and cancer-type specific expression profiles, making them highly attractive as therapeutic targets. Pan-cancer RNA sequencing data revealed broad expression of the SAMMSON lncRNA in uveal melanoma (UM), the most common primary intraocular malignancy in adults. Currently, there are no effective tr...
Preprint
Full-text available
Molecular phenotyping through shallow 3′-end RNA-sequencing workflows is increasingly applied in the context of large-scale chemical or genetic perturbation screens to study disease biology or support drug discovery. While these workflows enable accurate quantification of the most abundant genes, they are less effective for applications that requir...
Article
Full-text available
Spheroids are three-dimensional cellular models with widespread basic and translational application across academia and industry. However, methodological transparency and guidelines for spheroid research have not yet been established. The MISpheroID Consortium developed a crowdsourcing knowledgebase that assembles the experimental parameters of 3,0...
Preprint
Full-text available
Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Due to a lack of effective treatments, patients with metastatic disease have a median survival time of 6-12 months. We recently demonstrated that the SAMMSON long non-coding RNA (lncRNA) is essential for uveal melanoma cell survival and that antisense oligonucleotide (...
Article
Circular RNAs (circRNAs) are a class of endogenous noncoding RNAs that have been shown to play a role in normal development, homeostasis, and disease, including cancer. CircRNAs are formed through a process called back‐splicing, which results in a covalently closed loop with a nonlinear back‐spliced junction (BSJ). In general, circRNA BSJs are pred...
Preprint
The use of blood-based extracellular RNA (exRNA) as clinical biomarker requires the implementation of a validated procedure for sample collection, processing and profiling. So far, no study has systematically addressed the pre-analytical variables affecting transcriptome analysis of exRNAs. In the exRNAQC study, we evaluated 10 blood collection tub...
Preprint
Full-text available
Purpose Long non-coding RNAs (lncRNAs) can exhibit cell-type and cancer-type specific expression profiles, making them highly attractive as therapeutic targets. Pan-cancer RNA sequencing data revealed broad expression of the SAMMSON lncRNA in uveal melanoma (UM), the most common primary intraocular malignancy in adults. Currently, there are no effe...
Preprint
Full-text available
Technological advances in transcriptome sequencing of single cells continues to provide an unprecedented view on tissue composition and cellular heterogeneity. While several studies have compared different single cell RNA-seq methods with respect to data quality and their ability to distinguish cell subpopulations, none of these studies investigate...
Conference Paper
Liquid biopsies offer a minimally invasive alternative to tissue biopsies for both diagnosis and monitoring of treatment response. Extracellular RNAs present in biofluids have emerged as potential biomarkers in health and disease, including cancer. While current studies typically focus on plasma or serum, other biofluids may contain more informativ...
Conference Paper
p>Cancer biomarker studies require procedures that provide accurate and precise test results with high analytical sensitivity. Consequently, the growing use of extracellular RNA from human biofluids as clinically relevant biomarker requires the implementation of benchmarked methods for sample collection, processing, and profiling. While several sma...
Preprint
Full-text available
Extracellular RNAs present in biofluids have emerged as potential biomarkers for disease. Where most studies focus on plasma or serum, other biofluids may contain more informative RNA molecules, depending on the type of disease. Here, we present an unprecedented atlas of messenger, circular and small RNA transcriptomes of a comprehensive collection...
Article
Full-text available
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Article
Full-text available
Single cell RNA sequencing methods have been increasingly used to understand cellular heterogeneity. Nevertheless, most of these methods suffer from one or more limitations, such as focusing only on polyadenylated RNA, sequencing of only the 3' end of the transcript, an exuberant fraction of reads mapping to ribosomal RNA, and the unstranded nature...
Article
Full-text available
Long intergenic non-coding RNAs (lincRNAs) are emerging as integral components of signaling pathways in various cancer types. In neuroblastoma, only a handful of lincRNAs are known as upstream regulators or downstream effectors of oncogenes. Here, we exploit RNA sequencing data of primary neuroblastoma tumors, neuroblast precursor cells, neuroblast...
Preprint
Full-text available
Single cell RNA sequencing methods have been increasingly used to understand cellular heterogeneity. Nevertheless, most of these methods suffer from one or more limitations, such as focusing only on polyadenylated RNA, sequencing of only the 3 end of the transcript, an exuberant fraction of reads mapping to ribosomal RNA, and the unstranded nature...
Article
Full-text available
Wild-type p53 tumor suppressor activity in neuroblastoma tumors is hampered by increased MDM2 activity, making selective MDM2 antagonists an attractive therapeutic strategy for this childhood malignancy. Since monotherapy in cancer is generally not providing long-lasting clinical responses, we here aimed to identify small molecule drugs that synerg...
Article
Full-text available
The ongoing ascent of sequencing technologies has enabled researchers to gain unprecedented insights into the RNA content of biological samples. MiRNAs, a class of small non-coding RNAs, play a pivotal role in regulating gene expression. The discovery that miRNAs are stably present in circulation has spiked interest in their potential use as minima...
Poster
Impact of MDM2 SNP309 on the survival of neuroblastoma patients.
Article
Full-text available
Suppression of p53 activity is essential for proliferation and survival of tumor cells. A direct p53-activating compound, nutlin-3, was used in this study, together with p53 mutation analysis, to characterize p53 pathway defects in a set of 34 human neuroblastoma cell lines. We identified 9 cell lines (26%) with a p53 loss-of-function mutation, inc...
Poster
Concomitant inhibition of MDM2 and Aurora kinases induces synergistic antitumor effects in neuroblastoma cells.
Data
RDML file 1. Primer sequences of the MYCN and MYCN regulated genes and raw data from the expression analyses on the 6 neuroblastoma cell lines.
Data
Supplemental Figure S1. Frequency distribution (left-axis) and cumulative frequency (right-axis) of the difference in quantification cycle value (dCq) induced by sample pre-amplification (x-axis) for 194 genes measured in the 4 MAQC reference samples. There is a clear sequence-specific pre-amplification bias, meaning that some sequences or parts of...
Data
Supplemental Figure S4. Cumulative distribution plot of the delta-delta Cq (ddCq) before and after pre-amplification for 10 reference genes and 10 samples without purification of the pre-amplified product (black) and with purification of the pre-amplified product (grey). Each dot represents a ddCq-value between 2 samples before and after pre-amplif...
Data
Supplemental Figure S2. SPUD assay for the detection of enzymatic inhibitors in purified pre-amplified samples (P) and in non-purified pre-amplified samples (NP) with negative control (NC) and positives controls with known inhibitor (PC). Difference in Cq or delta-Cq (dCq) (NP or P vs. NC) < 1 indicates absence of enzymatic inhibitors.
Data
Supplemental Figure S3. PCR efficiencies estimated with two different single curve efficiency algorithms, PCR Miner (red) and LinReg (blue). Efficiencies of purified (squares; 2 replicates) and non-purified (triangles; 2 replicates) pre-amplified samples for each gene are comparable indicating that non-purified pre-amplified samples do not contain...
Data
RDML file 3. Primer sequences of HPRT1 and SDHA and raw data from the expression analyses on 738 neuroblastoma tumour samples.
Data
RDML file 2. Primer sequences of the MAQC target genes and raw data from the expression analyses on the 4 MAQC reference samples.
Data
Supplemental Material and Methods. Details on sample preparation, gene-expression analysis, formulas and raw data availability.
Article
Full-text available
Restoring p53 function by antagonizing its interaction with the negative regulator MDM2 is an appealing nongenotoxic approach to treating tumors with wild-type p53. Mutational inactivation of p53 is rare in neuroblastoma tumors at diagnosis and occurs in only a subset of multidrug-resistant neuroblastomas. The antiproliferative and cytotoxic effect...
Article
Full-text available
The quantitative polymerase chain reaction (qPCR) is a widely utilized method for gene-expression analysis. However, insufficient material often compromises large-scale gene-expression studies. The aim of this study is to evaluate an RNA pre-amplification method to produce micrograms of cDNA as input for qPCR. The linear isothermal Ribo-SPIA pre-am...
Article
Pinpointing critical regions of recurrent loss may help localize tumor suppressor genes. To determine the regions of loss on chromosome 3p in neuroblastoma, we performed loss of heterozygosity analysis using 16 microsatellite markers in a series of 65 primary tumors and 29 neuroblastoma cell lines. In this study, we report the results and discuss t...
Article
Full-text available
Chromosomal translocations involving the EVI1 locus are a recurrent finding in myeloid leukemia and are associated with poor prognosis. In this study, we performed a detailed molecular characterization of the recurrent translocation t(3;17)(q26;q22) in 13 hematologic malignancies. The EVI1 gene locus was rearranged in all 13 patients and was associ...
Article
CpG island hypermethylation has been recognized as an alternative mechanism for tumor suppressor gene inactivation. In this study, we performed methylation-specific PCR (MSP) to investigate the methylation status of 10 selected tumor suppressor genes in neuroblastoma. Seven of the investigated genes (CD44, RASSF1A, CASP8, PTEN, ZMYND10, CDH1, PRDM2...
Article
This article describes how rt-qPCR can be implemented as a tool to monitor silencing efficiency and functional effects of RNA interference (RNAi)-mediated gene knockdown, using examples from our research on neuroblastoma.
Article
The recurrent loss of 3p segments in neuroblastoma suggests the implication of 1 or more tumor suppressor genes but thus far few efforts have been made to pinpoint their detailed chromosomal position. To achieve this goal, array-based comparative genomic hybridization was performed on a panel of 23 neuroblastoma cell lines and 75 primary tumors usi...
Article
Full-text available
A correction to Human fetal neuroblast and neuroblastoma transcriptome analysis confirms neuroblast origin and highlights neuroblastoma candidate genes by K De Preter, J Vandesompele, P Heimann, N Yigit, S Beckman, A Schramm, A Eggert, RL Stallings, Y Benoit, M Renard, A De Paepe, G Laureys, S Påhlman and F Speleman. Genome Biology 2006 7:R84
Data
Corrected version of Additional data file 3 [1].
Data
Corrected version of Additional data file 2 [1].
Article
Full-text available
Circumvention of the p53 tumor suppressor barrier in neuroblastoma is rarely caused by TP53 mutation but might arise from inappropriately increased activity of its principal negative regulator MDM2. We show here that targeted disruption of the p53-MDM2 interaction by the small-molecule MDM2 antagonist nutlin-3 stabilizes p53 and selectively activat...
Data
Genes that are differentially expressed in neuroblast versus cortex samples, in neuroblast versus favorable (F) and/or unfavorable (UF) neuroblastoma, and in favorable versus unfavorable neuroblastoma
Data
Results of NBGS analysis of the genes that are differentially expressed between neuroblasts and (favorable and/or unfavorable) neuroblastomas (gene lists in Additional data file 1)
Data
RNA quality and quantity measures, validation of Affymetrix chip results, and Affymetrix chip quality parameters
Data
Genes of GO class neurogenesis and proneural genes that are expressed in neuroblast samples (> 36th percentile)
Article
Deletions of the short arm of chromosome 3 are often observed in a specific subset of aggressive neuroblastomas (NBs) with loss of distal 11q and without MYCN amplification. The critical deleted region encompasses the locus of the von Hippel-Lindau gene (VHL, 3p25). Constitutional loss of function mutations in the VHL gene are responsible for the V...
Article
In contrast to the well-documented involvement of EVI1 in various 3q26 aberrations, the transcriptional status of EVI1 in rare recurrent or sporadic 3q26 chromosomal defects has remained largely unexplored. Moreover, in a recent report, the association between 3q26 alterations in myeloid proliferations and ectopic EVI1 expression was questioned. Th...
Article
Full-text available
Neuroblastoma tumor cells are assumed to originate from primitive neuroblasts giving rise to the sympathetic nervous system. Because these precursor cells are not detectable in postnatal life, their transcription profile has remained inaccessible for comparative data mining strategies in neuroblastoma. This study provides the first genome-wide mRNA...
Article
We describe the molecular characterization of a t(7;9)(p15;q34) found in a 15-month-old female patient, diagnosed with refractory anemia with excess blasts in transformation (RAEBt), in progression to acute myeloid leukemia (AML) M7. Molecular characterization of the 7p15 breakpoint showed that this was localized within a fully sequenced PAC clone...
Article
Full-text available
It is often difficult to obtain good karyotypes of cells from children with acute lymphoblastic leukemia (ALL) because of poor morphology and spreading. Detailed karyotyping can be further hampered by the presence of multiple rearrangements. Our objective was to search for cryptic rearrangements in childhood ALL. A series of eight cases of childhoo...
Article
We present an extensive characterization of 10 B-cell lymphomas with a t(9;14)(p13;q32). The presence of the PAX5/IGH gene rearrangement was demonstrated by fluorescence in situ hybridization (FISH) using a validated probe set, whereas complex karyotypic changes were reassessed by multiplex-FISH (M-FISH). Pathologic and clinical review revealed the...
Article
Full-text available
Loss of chromosome 11q defines a subset of high-stage aggressive neuroblastomas. Deletions are typically large and mapping efforts have thus far not lead to a well defined consensus region, which hampers the identification of positional candidate tumour suppressor genes. In a previous study, functional evidence for a neuroblastoma suppressor gene o...
Article
Full-text available
Various types of mutations exist that exert an effect on the normal function of a gene. Among these, exon/gene deletions often remain unnoticed in initial mutation screening. Until recently, no fast and efficient methods were available to detect this type of mutation. Molecular detection methods for gene copy number changes included Southern blot (...
Article
Full-text available
MLL amplification was recently recognized as a recurrent aberration in acute myeloid leukemia (AML) and myelodys-plastic syndrome (MDS), associated with adverse prognosis and karyotype complexity. Here we present detailed results of fluorescence in situ hybridization (FISH) and expression analyses of MLL and 5 selected 11q candidate oncogenes (CBL,...

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