Cancer gene expression database (CGED): a database for gene expression profiling with accompanying clinical information of human cancer tissues

Kato, Kikuya

doi:10.1093/nar/gki117

Cited by 34 publications

(26 citation statements)

References 11 publications

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“…For statistical analysis, we used random control sets with 10,000 sites each as described previously [28]–[30]. Cancer-relative-genes which were directly hit by integration events or near (±5 kb) the integration sites were checked in a Cancer Gene Expression Databases (CGED, http://lifesciencedb.jp/cged/) [31].…”

Section: Methodsmentioning

confidence: 99%

Integration Profile and Safety of an Adenovirus Hybrid-Vector Utilizing Hyperactive Sleeping Beauty Transposase for Somatic Integration

et al. 2013

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We recently developed adenovirus/transposase hybrid-vectors utilizing the previously described hyperactive Sleeping Beauty (SB) transposase HSB5 for somatic integration and we could show stabilized transgene expression in mice and a canine model for hemophilia B. However, the safety profile of these hybrid-vectors with respect to vector dose and genotoxicity remains to be investigated. Herein, we evaluated this hybrid-vector system in C57Bl/6 mice with escalating vector dose settings. We found that in all mice which received the hyperactive SB transposase, transgene expression levels were stabilized in a dose-dependent manner and that the highest vector dose was accompanied by fatalities in mice. To analyze potential genotoxic side-effects due to somatic integration into host chromosomes, we performed a genome-wide integration site analysis using linker-mediated PCR (LM-PCR) and linear amplification-mediated PCR (LAM-PCR). Analysis of genomic DNA samples obtained from HSB5 treated female and male mice revealed a total of 1327 unique transposition events. Overall the chromosomal distribution pattern was close-to-random and we observed a random integration profile with respect to integration into gene and non-gene areas. Notably, when using the LM-PCR protocol, 27 extra-chromosomal integration events were identified, most likely caused by transposon excision and subsequent transposition into the delivered adenoviral vector genome. In total, this study provides a careful evaluation of the safety profile of adenovirus/Sleeping Beauty transposase hybrid-vectors. The obtained information will be useful when designing future preclinical studies utilizing hybrid-vectors in small and large animal models.

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Section: Methodsmentioning

confidence: 99%

Integration Profile and Safety of an Adenovirus Hybrid-Vector Utilizing Hyperactive Sleeping Beauty Transposase for Somatic Integration

et al. 2013

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“…Thus far, we have done gene expression profiling of a total of 1,200 human cancers using adaptor-tagged competitive PCR (ATAC-PCR), a PCR array system based on a high throughput reverse transcription-PCR technique (5 -7), and have constructed a cancer gene expression database that is open to the public (8). In this study, we did gene expression profiling on malignant gliomas to construct a prognostically useful diagnostic system for discriminating anaplastic oligodendroglioma from glioblastoma.…”

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confidence: 99%

Gene Expression-Based Molecular Diagnostic System for Malignant Gliomas Is Superior to Histological Diagnosis

Shirahata

Iwao-Koizumi

Saitō

et al. 2007

Clinical Cancer Research

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Purpose: Current morphology-based glioma classification methods do not adequately reflect the complex biology of gliomas, thus limiting their prognostic ability. In this study, we focused on anaplastic oligodendroglioma and glioblastoma, which typically follow distinct clinical courses. Our goal was to construct a clinically useful molecular diagnostic system based on gene expression profiling. Experimental Design: The expression of 3,456 genes in 32 patients, 12 and 20 of whom had prognostically distinct anaplastic oligodendroglioma and glioblastoma, respectively, was measured by PCR array. Next to unsupervised methods, we did supervised analysis using a weighted voting algorithm to construct a diagnostic system discriminating anaplastic oligodendroglioma from glioblastoma. The diagnostic accuracy of this system was evaluated by leave-one-out cross-validation. The clinical utility was tested on a microarray-based data set of 50 malignant gliomas from a previous study. Results: Unsupervised analysis showed divergent global gene expression patterns between the two tumor classes. A supervised binary classification model showed 100% (95% confidence interval, 89.4-100%) diagnostic accuracy by leave-one-out cross-validation using 168 diagnostic genes. Applied to a gene expression data set from a previous study, our model correlated better with outcome than histologic diagnosis, and also displayed 96.6% (28 of 29) consistency with the molecular classification scheme used for these histologically controversial gliomas in the original article. Furthermore, we observed that histologically diagnosed glioblastoma samples that shared anaplastic oligodendroglioma molecular characteristics tended to be associated with longer survival. Conclusions: Our molecular diagnostic system showed reproducible clinical utility and prognostic ability superior to traditional histopathologic diagnosis for malignant glioma.

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“…We previously performed gene expression profiling on more than a thousand cancer tissues by adaptor-tagged competitive PCR (ATAC-PCR) [10-14] for the Cancer Gene Expression Database (CGED) [15,16]. For each cancer type we performed middle-scale EST sequencing (the number of tags usually exceeded 5,000), and selected genes for assay among the expressed genes.…”

Section: Resultsmentioning

confidence: 99%

A novel technique for measuring variations in DNA copy-number: competitive genomic polymerase chain reaction

et al. 2007

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BackgroundChanges in genomic copy number occur in many human diseases including cancer. Characterization of these changes is important for both basic understanding and diagnosis of these diseases. Microarrays have recently become the standard technique and are commercially available. However, it is useful to have an affordable technique to complement them.ResultsWe describe a novel polymerase chain reaction (PCR)-based technique, termed competitive genomic PCR (CGP). The main characteristic of CGP is that different adaptors are added to the sample and control genomic DNAs after appropriate restriction enzyme digestion. These adaptor-supplemented DNAs are subjected to competitive PCR using an adaptor-primer and a locus-specific primer. The amplified products are then separated according to size differences between the adaptors. CGP eliminates the tedious steps inherent in quantitative PCR and achieves moderate throughput. Assays with different X chromosome numbers showed that it can provide accurate quantification. High-resolution analysis of neuroblastoma cell lines around the MYCN locus revealed novel junctions for amplification, which were not detected by a commercial array.ConclusionCGP is a moderate throughput technique for analyzing changes in genomic copy numbers. Because CGP can measure any genomic locus using PCR primers, it is especially useful for detailed analysis of a genomic region of interest.

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Cancer gene expression database (CGED): a database for gene expression profiling with accompanying clinical information of human cancer tissues

Cited by 34 publications

References 11 publications

Integration Profile and Safety of an Adenovirus Hybrid-Vector Utilizing Hyperactive Sleeping Beauty Transposase for Somatic Integration

Integration Profile and Safety of an Adenovirus Hybrid-Vector Utilizing Hyperactive Sleeping Beauty Transposase for Somatic Integration

Gene Expression-Based Molecular Diagnostic System for Malignant Gliomas Is Superior to Histological Diagnosis

A novel technique for measuring variations in DNA copy-number: competitive genomic polymerase chain reaction

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