Integrative analysis of neuroblastoma and pheochromocytoma genomics data
| Autor: | Miklós Pintér, Peter Igaz, Péter Szabó, Diana Rita Szabó, Adrienn Zsippai, Károly Rácz, Attila Patócs, András Falus |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Cooperative game theory
Adult lcsh:Internal medicine endocrine system von Hippel-Lindau Disease lcsh:QH426-470 endocrine system diseases In silico Statistics as Topic Adrenal Gland Neoplasms Multiple Endocrine Neoplasia Type 2a Pheochromocytoma Biology Bioinformatics Neuroblastoma Game Theory microRNA Databases Genetic Genetics medicine Cluster Analysis Humans Genetics(clinical) Von Hippel–Lindau disease lcsh:RC31-1245 neoplasms Genetics (clinical) Oligonucleotide Array Sequence Analysis Functional genomics Genomics medicine.disease Human genetics Gene Expression Regulation Neoplastic lcsh:Genetics Cancer research DNA microarray Research Article Signal Transduction |
| Zdroj: | BMC Medical Genomics BMC Medical Genomics, Vol 5, Iss 1, p 48 (2012) |
| ISSN: | 1755-8794 |
| Popis: | Background Pheochromocytoma and neuroblastoma are the most common neural crest-derived tumors in adults and children, respectively. We have performed a large-scale in silico analysis of altogether 1784 neuroblastoma and 531 pheochromocytoma samples to establish similarities and differences using analysis of mRNA and microRNA expression, chromosome aberrations and a novel bioinformatics analysis based on cooperative game theory. Methods Datasets obtained from Gene Expression Omnibus and ArrayExpress have been subjected to a complex bioinformatics analysis using GeneSpring, Gene Set Enrichment Analysis, Ingenuity Pathway Analysis and own software. Results Comparison of neuroblastoma and pheochromocytoma with other tumors revealed the overexpression of genes involved in development of noradrenergic cells. Among these, the significance of paired-like homeobox 2b in pheochromocytoma has not been reported previously. The analysis of similar expression patterns in neuroblastoma and pheochromocytoma revealed the same anti-apoptotic strategies in these tumors. Cancer regulation by stathmin turned out to be the major difference between pheochromocytoma and neuroblastoma. Underexpression of genes involved in neuronal cell-cell interactions was observed in unfavorable neuroblastoma. By the comparison of hypoxia- and Ras-associated pheochromocytoma, we have found that enhanced insulin like growth factor 1 signaling may be responsible for the activation of Src homology 2 domain containing transforming protein 1, the main co-factor of RET. Hypoxia induced factor 1α and vascular endothelial growth factor signaling included the most prominent gene expression changes between von Hippel-Lindau- and multiple endocrine neoplasia type 2A-associated pheochromocytoma. Conclusions These pathways include previously undescribed pathomechanisms of neuroblastoma and pheochromocytoma and associated gene products may serve as diagnostic markers and therapeutic targets. |
| Databáze: | OpenAIRE |
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