Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Array-CGH profiling of human neuroblastoma samples obtained from infants included in the INES99.1, INES99.2 and INES99.3 trials

ABSTRACT: In neuroblastoma (NB), the presence of segmental chromosome alterations (SCA) is associated with a higher risk of relapse, even when occurring together with numerical chromosome alterations (NCA). Furthermore, recent evidence shows that SCAs play a role in tumor progression. In order to analyze the role of SCAs in infants with NB, we have performed an extensive retrospective array-CGH analysis of tumours from infants enrolled in the European INES 99.1, 99.2 and 99.3 trials. Tumour samples from 221/300 enrolled patients could be analyzed. SCAs were observed in 11%, 20% and 59% of infants enrolled in trial 99.1 (localised unresectable NB), 99.2 (INSS stage 4s) and 99.3 (INSS stage 4), respectively (p<0.001), and were associated with the presence of bone metastasis (p<0.003). Progression-free survival was poorer in patients whose tumours harbored at least one SCA, in the whole population as well as in trials 99.1 and 99.2. In multivariate analysis, taking into account single genetic alterations, the protocol arm and genomic profile, the SCA genomic profile was the strongest predictor of poor outcome. Although overall survival was excellent, patients with stage 4s disease and a SCA genomic profile had a higher risk of relapse also in the absence of clinical symptoms at diagnosis and required a higher treatment burden for salvage. In conclusion, in infants with NB, a SCA genomic profile is useful to identify patients who will require upfront treatment even in the absence of other clinical indication for therapy, whereas an NCA genomic profile can identify a patient subpopulation in whom treatment reduction can be considered safe. Each of the 218 tumoral genomic DNAs was hybridized against non-tumoral DNA reference on BAC/PAC array or commercial supports in order to determine an overall genomic profile. The reference DNA was obtained from the blood of a single normal individual.

ORGANISM(S): Homo sapiens

SUBMITTER: Gudrun Schleiermacher

PROVIDER: E-GEOD-26494 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Publications

Segmental chromosomal alterations lead to a higher risk of relapse in infants with MYCN-non-amplified localised unresectable/disseminated neuroblastoma (a SIOPEN collaborative study).

Schleiermacher G G Michon J J Ribeiro A A Pierron G G Mosseri V V Rubie H H Munzer C C Bénard J J Auger N N Combaret V V Janoueix-Lerosey I I Pearson A A Tweddle D A DA Bown N N Gerrard M M Wheeler K K Noguera R R Villamon E E Cañete A A Castel V V Marques B B de Lacerda A A Tonini G P GP Mazzocco K K Defferrari R R de Bernardi B B di Cataldo A A van Roy N N Brichard B B Ladenstein R R Ambros I I Ambros P P Beiske K K Delattre O O Couturier J J

British journal of cancer 20111110 12

<h4>Background</h4>In neuroblastoma (NB), the presence of segmental chromosome alterations (SCAs) is associated with a higher risk of relapse.<h4>Methods</h4>In order to analyse the role of SCAs in infants with localised unresectable/disseminated NB without MYCN amplification, we have performed an array CGH analysis of tumours from infants enrolled in the prospective European INES trials.<h4>Results</h4>Tumour samples from 218 out of 300 enroled patients could be analysed. Segmental chromosome a ...[more]

PMID: 22146831

Similar Datasets

Project description:Neuroblastoma (NB) is an aggressive tumor that affects both infants and children. The disease outcome is greatly influenced by age of patient, stage, chromosome copy number aberrations (CNAs) and gene expression abnormalities. We analyzed, by microarray technology, genome and transcriptome of 3 groups of tumors of patients with metastatic disease: G1, stage 4S and MYCN single copy; G2, stage 4 younger than 18 months of age, MYCN single copy with no disease progression and G3, stage 4, older than 19 months, with unfavorable outcome. We found an accumulation of structural copy number aberrations (CNAs) in G3 whereas G1 tumors had mostly numerical (N) CNAs and G2 showed an intermediate behavior. Pair wise comparisons demonstrated that the average of N CNAs significantly decreased from G1 to G2 to G3 (9.6 G1 < 7.2 G2 < 3.6 G3); in contrast S CNAs significantly increased in G3 (0.7 G1 < 3.7 G2 < 7.0 G3). Interestingly, we observed several intra-chromosomal rearrangements in G3 tumors on chromosomes not usually involved in NB. Excluding MYCN amplified tumors by G3 we found a high frequency of S CNAs in this group. Gene expression analysis showed a deregulation of downstream genes of Ras and Rho signaling pathway among the 3 groups. It has been also observed a progressive switch off of development and adhesion genes and a switch on of cell cycle genes from G1 to G2 to G3. Moreover, the telemorase genes were significantly expressed in G3 with respect to remaining groups. Present data show an accumulation of S CNAs from stage 4S to 4. The deregulation of genes Rho/Ras pathway may explain the increase of tumor aggressiveness from G1 to G2 to G3. The increase of cell cycle and telomerase genes expression associated with G3 would provide unlimited replicative potential for these tumors and may be responsible for accumulation of S CNAs. Finally, we can argue that accumulation of structural aberrations and gene deregulation is age-dependent and it is associated with a more aggressive tumor phenotype. We analyzed 133 samples of metastatic neuroblastoma from patients divided into three groups: G1 49 patients stage 4S and MYCN single copy; G2 37 patients stage 4 younger than 18 months of age at diagnosis, MYCN single copy with no disease progression; G3 47 patients stage 4 older than 19 months of age at diagnosis, with unfavorable outcome.

Project description:The placenta, the complex of fetal membrane (the chorion is attached to the endometrium) and endometrium, is a highly specialized temporary organ responsible for the normal progression of pregnancy in mammals. Therefore, the endometrium was divided into two function regions: chorion-attached (CA) and non-chorion-attached (NCA) region. However, the difference in gene expression profiles between the CA and NCA endometrial tissue of mid-gestation still are unknown. The objective of this study was to reveal gene expressed profiles of the CA and NCA endometrium from the mid-gestational female rabbits, and to screen the differentially expressed genes (DEGs) to imply major physiological events of endometrial at mid-gestation. RNA-seq showed that a total of 12320 genes were co-expressed in the CA and NCA endometrium, and 646 DEGs were identified. Enrichment analysis of the DEGs revealed the top overrepresented gene ontology (GO) term and pathways were related to immune regulation, cellular adhesions. Furthermore, the expression levels of DEGs related to immune regulation of chemokines and their receptors, extracellular matrix (ECM) and Integrin, were compared between the CA and NCA endometrium. Overall, there was hardly difference in the expression levels of immune regulation genes (chemokines and their receptors) between the CA and NCA endometrium, while the concentration of IL-8, IL-6 and IL-1β in the CA endometrium was higher than that in the serum and the NCA endometrium, which suggested immune cytokines were accumulated in the endometrium of maternal-fetal interface. Meanwhile, the expression level of genes related to cellular adhesions (ECM-integrin) in the NCA endometrium was significantly higher than that in the CA endometrium, and high abundance of Integrin β and THBS1 were localized in the luminal epithelium of the NCA endometrium, but not in the CA endometrium. Conclusions: Our study revealed the gene expression profiles of the CA and the NCA endometrium at mid-gestation, and provides an implication of chemokine and ECM-Integrin involved in immune regulation and adhesive barrier at the endometrium.

Project description:Neuroblastoma (NB) is an embryonal tumor with various clinical presentations and behaviors. Several genomic alterations has been well-studied in NB, among which genomic amplification of MYCN oncogene, is a strong prognostic biomarker with worsens outcome. Long noncoding RNAs (lncRNAs), constitute major proportion of the cellular transcripts with no coding capacity. One of their function is to guide transcription factors to the target genes and facilitate gene expression. However, relative contribution of lncRNA and MYCN to the advanced NB has remained unclear. Herein, by applying a network-based integrative analysis on MYCN amplified and MYCN nonamplified lncRNA expression profile from both RNA-seq and microarray platform, we identified lncRNA, SNHG1 to be differentially expressed and strongly correlated with MYCN in MYCN-amplified NB. The expression of SNHG1 was validated by RT-qPCR in NB cell lines. Survival analysis revealed that higher expression of SNHG1 significantly associates with poor patient survival. Moreover, knockdown of MYCN in MYCN-amplified NB cell lines inhibited SNHG1 expression. Furthermore, to unravel the role of SNHG1 in NB, we extracted SNHG1-interacting proteins by RNA-protein pull down assay coupled with doi:10.6342/NTU201701980 ! ! VI liquid chromatography-tandem mass spectrometry (LC-MS/MS). We identified 27 SNHG1-interacting proteins in common from three NB cell lines. However, only three SNHG1-interacting proteins, MATR3, YBX1 and HHRNPL have binding site detected by DeepBind motif analysis. Western blot confirms interaction of MATR3 with SNHG1. Additionally, we further validated the direct interaction between MATR3 and SNHG1 by RNA-immunoprecipation (IP). MATR3 is known to be involved in RNA transport and stabilization. Therefore, we proposed that MATR3 after interacting with SNHG1 might help in SNHG1 transcription and stabilization. In conclusion, our study unveils that SNHG1 could be a prognostic marker for high-risk NB and possibly stabilized by MATR3. Our results might provide future directions for the development of therapeutic strategies against high-risk NB.

Dataset Information

Array-CGH profiling of human neuroblastoma samples obtained from infants included in the INES99.1, INES99.2 and INES99.3 trials

Publications

Segmental chromosomal alterations lead to a higher risk of relapse in infants with MYCN-non-amplified localised unresectable/disseminated neuroblastoma (a SIOPEN collaborative study).

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets