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Integrated bioinformatic and wet-lab approach to identify potential oncogenic networks in neuroblastoma: MEIS1

ABSTRACT: The pediatric tumor neuroblastoma is the second cause of cancer-related death in children. Although several recurrent gene aberrations have been found, the main signaling networks in the neuroblastoma cell, that can give important clues for more specific, more efficient treatment, is still unknown. Here we demonstrate an analysis of the MEIS1 pathway in neuroblastic tumors. It suggests important regulatory connections to tumor differentiation, cell cycle, and cell death.

ORGANISM(S): Homo sapiens

PROVIDER: GSE17827 | GEO | 2012/09/24

SECONDARY ACCESSION(S): PRJNA123295

REPOSITORIES: GEO

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Integrated bioinformatic and wet-lab approach to identify potential oncogenic networks in neuroblastoma: MEIS1

Project description:The pediatric tumor neuroblastoma is the second cause of cancer-related death in children. Although several recurrent gene aberrations have been found, the main signaling networks in the neuroblastoma cell, that can give important clues for more specific, more efficient treatment, is still unknown. Here we demonstrate an analysis of the MEIS1 pathway in neuroblastic tumors. It suggests important regulatory connections to tumor differentiation, cell cycle, and cell death. Time-course experiment of MEIS1-shRNA induction, with 5 timepoints.

2012-09-24 | E-GEOD-17827 | biostudies-arrayexpress

Integrated bioinformatic and wet-lab approach to identify potential oncogenic networks in neuroblastoma

Project description:mRNA profiles of thousands of human tumors are available, but methods to deduce oncogenic signaling networks from these data lag behind. It is especially challenging to identify main-regulatory routes, and to generalize conclusions obtained from experimental models. We designed the bioinformatic platform R2 in parallel with a wet-lab approach of neuroblastoma. Here we demonstrate how R2 facilitates an integrated analysis of our neuroblastoma data. Analysis of the MYCN pathway suggested important regulatory connections to the polyamine synthesis route, the Notch pathway and the BMP/TGFM-NM-2 pathway. A network of genes emerged connecting major oncogenes in neuroblastoma. Genes in the network carried strong prognostic values and were essential for tumor cell survival. 88 human Neuroblastoma samples were analyzed.

2012-03-08 | E-GEOD-16476 | biostudies-arrayexpress

Integrated bioinformatic and wet-lab approach to identify potential oncogenic networks in neuroblastoma

Project description:mRNA profiles of thousands of human tumors are available, but methods to deduce oncogenic signaling networks from these data lag behind. It is especially challenging to identify main-regulatory routes, and to generalize conclusions obtained from experimental models. We designed the bioinformatic platform R2 in parallel with a wet-lab approach of neuroblastoma. Here we demonstrate how R2 facilitates an integrated analysis of our neuroblastoma data. Analysis of the MYCN pathway suggested important regulatory connections to the polyamine synthesis route, the Notch pathway and the BMP/TGFβ pathway. A network of genes emerged connecting major oncogenes in neuroblastoma. Genes in the network carried strong prognostic values and were essential for tumor cell survival.

2012-03-08 | GSE16476 | GEO

Integrated bioinformatic and wet-lab approach to identify potential oncogenic networks in neuroblastoma: MYCN

Project description:mRNA profiles of thousands of human tumors are available, but methods to deduce oncogenic signaling networks from these data lag behind. It is especially challenging to identify main-regulatory routes, and to generalize conclusions obtained from experimental models. We designed the bioinformatic platform R2 (http://r2.amc.nl) in parallel with a wet-lab approach of neuroblastoma. Here we demonstrate how R2 facilitates an integrated analysis of our neuroblastoma data. Analysis of the MYCN pathway suggested important regulatory connections to the polyamine synthesis route, the Notch pathway and the BMP/TGFÎ² pathway. A network of genes emerged connecting major oncogenes in neuroblastoma. Genes in the network carried strong prognostic values and were essential for tumor cell survival. Time-course experiments in triplicate of MYCN induction after doxycycline addition, with 7 timepoints.

2015-10-20 | E-GEOD-16478 | biostudies-arrayexpress

Integrated bioinformatic and wet-lab approach to identify potential oncogenic networks in neuroblastoma: MSX1

Project description:mRNA profiles of thousands of human tumors are available, but methods to deduce oncogenic signaling networks from these data lag behind. It is especially challenging to identify main-regulatory routes, and to generalize conclusions obtained from experimental models. We designed the bioinformatic platform R2 (http://r2.amc.nl) in parallel with a wet-lab approach of neuroblastoma. Here we demonstrate how R2 facilitates an integrated analysis of our neuroblastoma data. Analysis of the MYCN pathway suggested important regulatory connections to the polyamine synthesis route, the Notch pathway and the BMP/TGFM-NM-2 pathway. A network of genes emerged connecting major oncogenes in neuroblastoma. Genes in the network carried strong prognostic values and were essential for tumor cell survival. Triplicate time course experiments of MSX1 induction, with 4 timepoints.

2014-05-28 | E-GEOD-16481 | biostudies-arrayexpress

Integrated bioinformatic and wet-lab approach to identify potential oncogenic networks in neuroblastoma: MYCN

Project description:mRNA profiles of thousands of human tumors are available, but methods to deduce oncogenic signaling networks from these data lag behind. It is especially challenging to identify main-regulatory routes, and to generalize conclusions obtained from experimental models. We designed the bioinformatic platform R2 (http://r2.amc.nl) in parallel with a wet-lab approach of neuroblastoma. Here we demonstrate how R2 facilitates an integrated analysis of our neuroblastoma data. Analysis of the MYCN pathway suggested important regulatory connections to the polyamine synthesis route, the Notch pathway and the BMP/TGFβ pathway. A network of genes emerged connecting major oncogenes in neuroblastoma. Genes in the network carried strong prognostic values and were essential for tumor cell survival.

2015-10-20 | GSE16478 | GEO

Integrated bioinformatic and wet-lab approach to identify potential oncogenic networks in neuroblastoma: MSX1

Project description:mRNA profiles of thousands of human tumors are available, but methods to deduce oncogenic signaling networks from these data lag behind. It is especially challenging to identify main-regulatory routes, and to generalize conclusions obtained from experimental models. We designed the bioinformatic platform R2 (http://r2.amc.nl) in parallel with a wet-lab approach of neuroblastoma. Here we demonstrate how R2 facilitates an integrated analysis of our neuroblastoma data. Analysis of the MYCN pathway suggested important regulatory connections to the polyamine synthesis route, the Notch pathway and the BMP/TGFβ pathway. A network of genes emerged connecting major oncogenes in neuroblastoma. Genes in the network carried strong prognostic values and were essential for tumor cell survival.

2014-05-28 | GSE16481 | GEO

Analysis of TALE homeobox genes in neuroblastic tumors: ganglioneuroblastoma and ganglioneuroma

Project description:A large proportion of patients suffering from the malignant pediatric tumor neuroblastoma die of progressive disease despite intensive therapy. Neuroblastomas belong to the group of neuroblastic tumors, together with the more benign, differentiated ganglioneuroblastomas and ganglioneuromas. Little is known of the genes driving the differentiation processes in these tumor types. A search for the transcription factors differentially expressed between ganglioneuromas, ganglioneuroblastomas, and neuroblastomas in a series of 110 neuroblastic tumors (NB110) identified a large number of HOX- and TALE (Three Amino acid Loop Extension)-class homeobox transcription factor genes. The MEIS1-3, PBX1 and -3, and PKNOX1 TALE genes showed highest expression in neuroblastomas and lowest in ganglioneuromas and ganglioneuroblastomas. The PKNOX2 and TGIF1-2 genes showed the opposite expression pattern. This suggests an involvement of TALE genes in neuroblastoma differentiation. Expression of MEIS1, a known oncogene in haematopoietic tumors, was high in all neuroblastomas, and strongly correlated with undifferentiated histology. Consequently, we generated IMR-32 neuroblastoma cells capable of inducible shRNA-mediated MEIS1 knockdown. We observed differentiation, growth arrest and induction of apoptosis upon MEIS1 down-regulation. Affymetrix profiling of time-course experiments using these cells allowed the identification of MEIS1 target genes. Analysis of the target genes in the NB110 series showed that 323 of these were also significantly correlated to MEIS1 expression and to tumor differentiation in neuroblastic tumors. Genes involved in the cell cycle and in developmental pathways were over-represented in this gene set. We conclude that MEIS1 governs several of the signal transduction routes important for neuroblastoma survival and differentiation. 12 ganglioneuroma (gn) and 10 ganglioneuroblastoma (gnb) were analyzed.

2012-09-24 | E-GEOD-18271 | biostudies-arrayexpress

Analysis of TALE homeobox genes in neuroblastic tumors: ganglioneuroblastoma and ganglioneuroma

2012-09-24 | GSE18271 | GEO

Analysis of TALE homeobox genes in neuroblastic tumors and Cell lines

Project description:This SuperSeries is composed of the following subset Series: GSE17827: Integrated bioinformatic and wet-lab approach to identify potential oncogenic networks in neuroblastoma: MEIS1 GSE18271: Analysis of TALE homeobox genes in neuroblastic tumors: ganglioneuroblastoma and ganglioneuroma Refer to individual Series

2012-09-24 | E-GEOD-18272 | biostudies-arrayexpress

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