Molecular Profiling Identifies Prognostic Subgroups of Pediatric Glioblastoma and Shows Increased YB-1 Expression in Tumors
| العنوان: | Molecular Profiling Identifies Prognostic Subgroups of Pediatric Glioblastoma and Shows Increased YB-1 Expression in Tumors |
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| المؤلفون: | Sandra E. Dunn, Stephen Albrecht, Martin E. Gleave, Elvis Terci Valera, Anne Sophie Carret, László Bognár, Pawel P. Liberski, Rolando F. Del Maestro, Nada Jabado, Luis G. Tone, André Nantel, Damien Faury, Miklós Garami, Zoltán Hanzély, Torsten Pietsch, Peter Hauser, Jose Luis Montes, Takrima Haque, Marie-Christine Guiot, Enrique López-Aguilar |
| المصدر: | Journal of Clinical Oncology. 25:1196-1208 |
| بيانات النشر: | American Society of Clinical Oncology (ASCO), 2007. |
| سنة النشر: | 2007 |
| مصطلحات موضوعية: | Male, Cancer Research, Pathology, Gene Expression, Apoptosis, Polymerase Chain Reaction, Gene expression, Phosphorylation, Child, Aged, 80 and over, Brain Neoplasms, Brain, Nuclear Proteins, Middle Aged, Prognosis, Immunohistochemistry, Phenotype, DNA-Binding Proteins, ErbB Receptors, Oncology, Child, Preschool, Female, Signal transduction, Signal Transduction, Adult, medicine.medical_specialty, Adolescent, Brain tumor, methods, Proto-Oncogene Proteins p21(ras), Proto-Oncogene Proteins, medicine, pharmaceutical, Humans, genome, Gene, PI3K/AKT/mTOR pathway, Aged, Epidermal Growth Factor, business.industry, Protein, Gene Expression Profiling, Proteins, Infant, medicine.disease, Gene expression profiling, Genes, Cancer research, Y-Box-Binding Protein 1, Glioblastoma, business, Proto-Oncogene Proteins c-akt |
| الوصف: | Purpose Pediatric glioblastoma (pGBM) is a rare, but devastating brain tumor. In contrast to GBM in adults (aGBM), little is known about the mechanisms underlying its development. Our aim is to gain insight into the molecular pathways of pGBM. Materials and Methods Thirty-two pGBM and seven aGBM samples were investigated using biochemical and transcriptional profiling. Ras and Akt pathway activation was assessed through the phosphorylation of downstream effectors, and gene expression profiles were generated using the University Health Network Human 19K cDNA arrays. Results were validated using real-time polymerase chain reaction and immunohistochemistry and compared with existing data sets on aGBM. Results There are at least two subsets of pGBM. One subset, associated with Ras and Akt pathway activation, has very poor prognosis and exhibits increased expression of genes related to proliferation and to a neural stem-cell phenotype, similar to findings in aggressive aGBM. This subset was still molecularly distinguishable from aGBM after unsupervised and supervised analysis of expression profiles. A second subset, with better prognosis, is not associated with activation of Akt and Ras pathways, may originate from astroglial progenitors, and does not express gene signatures and markers shown to be associated with long-term survival in aGBM. Both subsets of pGBM show overexpression of Y-box-protein-1 that may help drive oncogenesis in this tumor. Conclusion Our work, the first study of gene expression profiles in pGBM, provides valuable insight into active pathways and targets in a cancer with minimal survival, and suggests that these tumors cannot be understood exclusively through studies of aGBM. |
| تدمد: | 1527-7755 0732-183X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::03df64689fcb85e74062e45d25ddd86aTest https://doi.org/10.1200/jco.2006.07.8626Test |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....03df64689fcb85e74062e45d25ddd86a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15277755 0732183X |
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