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Pilot-study for a novel universal tool for detection of oncogenic fusion transcripts

ABSTRACT: A novel oligonucleotide microarray design is described whereby one can screen for all known oncogenic fusion transcripts by one microarray hybridization. Measurements of chimeric transcript junctions are combined with exon-wise measurements of individual fusion partners. Keywords: Nimblegen custom-design

ORGANISM(S): Homo sapiens

PROVIDER: GSE14435 | GEO | 2009/01/19

SECONDARY ACCESSION(S): PRJNA111769

REPOSITORIES: GEO

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Pilot-study for a novel universal tool for detection of oncogenic fusion transcripts

Project description:A novel oligonucleotide microarray design is described whereby one can screen for all known oncogenic fusion transcripts by one microarray hybridization. Measurements of chimeric transcript junctions are combined with exon-wise measurements of individual fusion partners. Keywords: Nimblegen custom-design The pilot data included a design with 68,861 oligonucleotide probes covering all combinations of chimeric exon-exon junctions from 275 pairs of fusion genes, as well as sets of oligos internal to all the exons of the fusion partners. Proof of principle was demonstrated by detection of known fusion genes (such as TCF3:PBX1, ETV6:RUNX1, and TMPRSS2:ERG) from six positive controls consisting of leukemia cell lines and prostate cancer biopsies.

2010-05-06 | E-GEOD-14435 | biostudies-arrayexpress

FUSION Cohort Study

Project description:FUSION Cohort Study

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Menin-MLL inhibitors block oncogenic transformation by MLL fusion proteins in a fusion partner independent manner

Project description:Chromosomal rearrangements of the Mixed Lineage Leukemia (MLL) gene result in fusion proteins which retain the N-terminal portion of MLL fused with one of more than 70 different fusion partners. The high diversity of MLL fusion partners raises a question whether it is possible to develop a general therapeutic strategy to block the oncogenic activity of MLL fusion proteins in a fusion partner independent manner. We have demonstrated that blocking the menin-MLL interaction using small molecule inhibitor inhibits oncogenic activity of different MLL fusion proteins according to a mechanism that is independent on the fusion partner.

2018-06-09 | GSE69740 | GEO

Hereditary Hearing Loss SNP-Microarray Pilot Study

Project description:Objectives: Despite recent advancements in diagnostic tools, the genomic landscape of hereditary hearing loss remains largely uncharacterized. One strategy to understand genome-wide aberrations includes the analysis of copy number variation that can be mapped using SNP-microarray technology. A growing collection of literature has begun to uncover the importance of copy number variation in hereditary hearing loss. This pilot study underpins a larger effort that involves the stage-wise analysis of hearing loss patients, many of whom have advanced to high-throughput sequencing analysis. Data description: Our data originate from Infinium HumanOmni1-Quad v1.0 SNP-microarrays (Illumina) that provide useful markers for genome-wide association studies and copy number variation analysis. This dataset comprises a cohort of 108 individuals (99 with hearing loss, 9 normal hearing family members) for the purpose of understanding the genetic contribution of copy number variations to hereditary hearing loss.

2018-03-06 | GSE111131 | GEO

Large scale screening for fusion genes in sarcoma patient samples

Project description:We have utilized our custom array GPL11054 to screen a set of sarcoma patient samples for fusion genes One negative control was included in the study. We wanted to investigate the power of our fusion-gene array GPL11054 as a means for fusion gene detection in a series of sarcoma patient samples from two diagnostic laboratories with expertise in fusion gene detection.

2013-10-23 | E-GEOD-43632 | biostudies-arrayexpress

Expression Profiling of human Fusion-Positive and Fusion-Negative Rhabdomyosarcoma

Project description:Genome-wide gene expression in 33 fusion-positive and 25 fusion-negative rhabdomyosarcoma cases was studied using GeneChip Human Genome U133 Plus2 (Affymetrix) Fusion-positive versus fusion-negative rhabdomyosarcoma tumors

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Fusion partner directed chromatin occupancy drives the transcriptome heterogeneity of MLL-fusion acute lymphoblastic leukemia

Project description:Fusion of the N-terminus of the mixed-lineage-leukemia (MLL) gene with various partner genes drives acute lymphoblastic leukemia (ALL). Despite the fusion proteins sharing some common attributes, transcriptome heterogeneity of MLL-fusion ALL is observed and the underlying mechanism and biological consequences are unknown. We compared the genome-wide occupancy of MLL-Af4 and MLL-AF9 in human ALL cells expressing FLAG-tagged fusion proteins. Although both oncoproteins retain the same MLL N-terminal domains that mediate chromatin binding, the two fusion proteins displayed largely non-overlapping binding profiles, with MLL-AF9 showing preferential binding at repetitive elements. The binding specificity of each fusion protein was associated with differential global gene activation distinguishing the two ALLs. A subset of prednisolone response genes were among the differentially regulated targets, and the resistance related genes were specifically upregulated in MLL-Af4/AF4 cells. These studies provide evidence that distinct chromatin occupancy of different MLL-fusion proteins is one driving force for transcriptome heterogeneity of MLL-fusion ALL, which could potentially result in the disparate therapeutic outcome of the disease.

2018-04-30 | GSE103947 | GEO

Gene expression profiling as a tool for sediment risk assessment: a pilot study using Caenorhabditis elegans whole genome microarrays

Project description:Toxicity of river sediments are assessed using whole sediment toxicity tests with benthic organisms. The challenge, however, is the differentiation between multiple effects caused by complex contaminant mixtures and the unspecific toxicity endpoints such as survival, growth or reproduction. Moreover, natural sediment properties, such as grain size distribution and organic carbon content, can influence the test parameters by masking pollutant toxicity. The use of gene expression profiling facilitates the identification of transcriptional changes at the molecular level that are specific to the bioavailable fraction of pollutants. The nematode Caenorhabditis elegans is ideally suited for these purposes, as (i) it can be exposed to whole sediments, and (ii) its genome is fully sequenced and widely annotated. In this pilot study we exposed C. elegans for 48 h to three sediments varying in degree of contamination with e.g. heavy metals and organic pollutants. Following the exposure period, gene expression was profiled using a whole genome DNA-microarray approach. Whole genome DNA microarray experiments were performed using a common reference design to identify differentially expressed genes in nematodes exposed to one of three river sediments of differing pollution level. Each sample consists of the 5 “biological replicates”.

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Study of Seribantumab in Adult Patients With NRG1 Gene Fusion Positive Advanced Solid Tumors

Project description:This study is an open-label, international, multi-center, Phase 2 study in adult patients with recurrent, locally-advanced or metastatic solid tumors, which harbor the NRG1 gene fusion.

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Large scale screening for known fusion genes in cancer cell lines

Project description:We have utilized a version 2.0 of our Fusion gene microarray (version 1.0 described by PMID: 19152679 and GEO, GPL8078) to screen cancer cell lines for known fusion genes We assembled a comprehensive database of published fusion genes, including those which have been reported only in individual studies and samples, and fusion genes resulting from deep sequencing of cancer genomes and transcriptomes. From the total set of 548 fusion genes, we designed 197,846 unique oligonucleotides, targeting both chimeric transcript junctions as well as sequences internal to each of the fusion gene partners. We investigated the presence of fusion genes in a series of 67 cell lines originating from 15 different cancer types. Data from ten leukaemia cell lines with known fusion gene status were used to evaluate and calibrate an automated scoring algorithm. In five out of ten cell lines the correct fusion gene was the top most scoring hit, and one came second, all six passing a cut-off of 50 percent of theoretical maximum-score. Two additional fusion genes, BCAS4-BCAS3 from the MCF-7 breast cancer cell line and CCDC6-RET from the TPC-1 thyroid cancer cell line were validated as true positive fusion transcripts from the remaining 57 cell lines. A total of 67 cell lines from various cancer types were analysed for presence of known fusion genes

2011-02-10 | E-GEOD-24737 | biostudies-arrayexpress

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