American Association for Cancer Research
10780432ccr100613-sup-ccr_10-0613_primers_pdf_6k.pdf (6.92 kB)

Supplement 1 from Gene Expression Analysis Identifies Potential Biomarkers of Neurofibromatosis Type 1 Including Adrenomedullin

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journal contribution
posted on 2023-03-31, 16:22 authored by Trent R. Hummel, Walter J. Jessen, Shyra J. Miller, Lan Kluwe, Victor F. Mautner, Margaret R. Wallace, Conxi Lázaro, Grier P. Page, Paul F. Worley, Bruce J. Aronow, Elizabeth K. Schorry, Nancy Ratner

PDF file - 6K, List of the forward and reverse quantitative real-time PCR primers are shown in Supplement 1.



Purpose: Plexiform neurofibromas (pNF) are Schwann cell tumors found in a third of individuals with neurofibromatosis type 1 (NF1). pNF can undergo transformation to malignant peripheral nerve sheath tumors (MPNST). There are no identified serum biomarkers of pNF tumor burden or transformation to MPNST. Serum biomarkers would be useful to verify NF1 diagnosis, monitor tumor burden, and/or detect transformation.Experimental Design: We used microarray gene expression analysis to define 92 genes that encode putative secreted proteins in neurofibroma Schwann cells, neurofibromas, and MPNST. We validated differential expression by quantitative reverse transcription-PCR, Western blotting, and ELISA assays in cell conditioned medium and control and NF1 patient sera.Results: Of 13 candidate genes evaluated, only adrenomedullin (ADM) was confirmed as differentially expressed and elevated in serum of NF1 patients. ADM protein concentrati on was further elevated in serum of a small sampling of NF1 patients with MPNST. MPNST cell conditioned medium, containing ADM and hepatocyte growth factor, stimulated MPNST migration and endothelial cell proliferation.Conclusions: Thus, microarray analysis identifies potential serum biomarkers for disease, and ADM is a serum biomarker of NF1. ADM serum levels do not seem to correlate with the presence of pNFs but may be a biomarker of transformation to MPNST. Clin Cancer Res; 16(20); 5048–57. ©2010 AACR.

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