Integrative Genomic Analyses of Neurofibromatosis Tumours Identify SOX9 As a Biomarker and Survival Gene

Overview

Journal EMBO Mol Med

Specialty Molecular Biology

Date 2010 Jan 6

PMID 20049725

Citations 74

Authors

Shyra J Miller

Walter J Jessen

Tapan Mehta

Atira Hardiman

Emily Sites

Sergio Kaiser

Anil G Jegga

Hua Li

Meena Upadhyaya

Marco Giovannini

David Muir

Margaret R Wallace

Eva Lopez

Eduard Serra

G Petur Nielsen

Conxi Lazaro

Anat Stemmer-Rachamimov

Grier Page

Bruce J Aronow

Nancy Ratner

Affiliations

Soon will be listed here.

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.

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