Integrative genomic analyses of neurofibromatosis tumours identify SOX9 as A biomarker and survival gene
| Autor: | Conxi Lázaro, Anil G. Jegga, Margaret R. Wallace, Eduard Serra, Tapan Mehta, Shyra J. Miller, G. Petur Nielsen, Grier P. Page, Meena Upadhyaya, Hua Li, Walter J. Jessen, Emily Sites, Bruce J. Aronow, Eva López, David Muir, Atira Hardiman, Marco Giovannini, Nancy Ratner, Anat Stemmer-Rachamimov, Sergio Kaiser |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Pathology
medicine.medical_specialty Neurofibromatosis 1 Schwann cell SOX9 Biology neurofibroma Neurofibromatosis 03 medical and health sciences 0302 clinical medicine Peripheral Nervous System Neoplasms Cell Line Tumor medicine Biomarkers Tumor Neurofibroma Humans malignant peripheral nerve sheath tumour Cells Cultured 030304 developmental biology Tumors Regulation of gene expression 0303 health sciences Neurofibromatosi Gene Expression Profiling Biochemical markers Neural crest SOX9 Transcription Factor medicine.disease Gene expression profiling Gene Expression Regulation Neoplastic medicine.anatomical_structure Cell culture 030220 oncology & carcinogenesis Marcadors bioquímics Cancer research Molecular Medicine Schwann Cells Closeup Sox9 |
| Zdroj: | Dipòsit Digital de la UB Universidad de Barcelona Recercat. Dipósit de la Recerca de Catalunya instname EMBO Molecular Medicine |
| Popis: | Understanding the biological pathways critical for common neurofibromatosis type 1 (NF1) peripheral nerve tumours is essential, as there is a lack of tumour biomarkers, prognostic factors and therapeutics. We used gene expression profiling to define transcriptional changes between primary normal Schwann cells (n = 10), NF1-derived primary benign neurofibroma Schwann cells (NFSCs) (n = 22), malignant peripheral nerve sheath tumour (MPNST) cell lines (n = 13), benign neurofibromas (NF) (n = 26) and MPNST (n = 6). Dermal and plexiform NFs were indistinguishable. A prominent theme in the analysis was aberrant differentiation. NFs repressed gene programs normally active in Schwann cell precursors and immature Schwann cells. MPNST signatures strongly differed; genes up-regulated in sarcomas were significantly enriched for genes activated in neural crest cells. We validated the differential expression of 82 genes including the neural crest transcription factor SOX9 and SOX9 predicted targets. SOX9 immunoreactivity was robust in NF and MPSNT tissue sections and targeting SOX9 - strongly expressed in NF1-related tumours - caused MPNST cell death. SOX9 is a biomarker of NF and MPNST, and possibly a therapeutic target in NF1. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|