Integrative genomic analyses of neurofibromatosis tumours identify SOX9 as a biomarker and survival gene
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Author
Miller, Shyra J
Jessen, Walter J
Mehta, Tapan
Hardiman, Atira
Sites, Emily
Kaiser, Sergio
Jegga, Anil G
Upadhyaya, Meena
Giovannini, Marco
Wallace, Margaret R
Lopez, Eva
Serra, Eduard
Lazaro, Conxi
Page, Grier
Aronow, Bruce J
Ratner, Nancy
Li, Hua
Muir, David
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.1002/emmm.200900027Metadata
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Miller, Shyra J, Walter J Jessen, Tapan Mehta, Atira Hardiman, Emily Sites, Sergio Kaiser, Anil G Jegga, et al. 2009. Integrative genomic analyses of neurofibromatosis tumours identify SOX9 as a biomarker and survival gene. EMBO Molecular Medicine 1(4): 236-248.Abstract
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.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3378132/pdf/Terms of Use
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