Open AccessIntegrative genomic analyses of neurofibromatosis tumours identify SOX9 as a biomarker and survival gene
Author(s) -
Miller Shyra J.,
Jessen Walter J.,
Mehta Tapan,
Hardiman Atira,
Sites Emily,
Kaiser Sergio,
Jegga Anil G.,
Li Hua,
Upadhyaya Meena,
Giovannini Marco,
Muir David,
Wallace Margaret R.,
Lopez Eva,
Serra Eduard,
Nielsen G. Petur,
Lazaro Conxi,
StemmerRachamimov Anat,
Page Grier,
Aronow Bruce J.,
Ratner Nancy
Publication year - 2009
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.1002/emmm.200900027
Subject(s) - sox10 , neural crest , neurofibromatosis , cancer research , plexiform neurofibroma , neurofibroma , biology , sox9 , schwann cell , pathology , gene expression profiling , transcription factor , gene expression , gene , medicine , microbiology and biotechnology , genetics
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.