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Neurofibromatosis type 1 is a genetic condition that can cause tumors to form on nerves under the skin. Since these tumors can become malignant, it is important to monitor their growth closely and detect signs of malignant transformation as early as possible. However, the only way to currently detect them is with an MRI scan. New research published in BioMed Central’s open access journal BMC Medicine shows that a simple blood test for the protein melanoma-inhibitory activity (MIA) may be used to indicate the presence of neurofibromas even if they cannot be seen .
Neurofibromatosis (NF) is a genetically-inherited disorder that causes tumors to grow on nerve tissue. There are three main types of NF tumors: neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2) and schwannomatosis. NF1 is the most frequent of the three tumor types affecting one in every 3,000 people. The severity of symptoms range from benign ‘cafe au lait’ patches on the skin, to small dermal tumors on the surface of the skin, to larger “plexiform” neurofibromas that are associated with deep nerve structures, to malignant tumors of the nerve sheath.
Previous studies have shown that loss of the gene neurofibromin (Nf1) during mouse embryo development causes defects in bone and cartilage development [2-3]. One of the observed changes was an increase in the expression of the transcription factor SRY-BOX 9 (SOX9), which regulates cartilage differentiation and was recently found to be highly expressed in NF1-related tumors supporting cell survival . German researchers hypothesized that some of the cartilage specific genes regulated by SOX9 might prove to be relevant biomarkers of NF1 tumors. They tested this hypothesis by analyzing expression of the SOX9 target gene melanoma-inhibitory activity (MIA) in tumor and serum samples from NF1 patients.
In a mouse Nf1 model, Mia was expressed at higher levels than in control mice. In humans, MIA was expressed in all tumors from NF1 patients. MIA serum level was determined in 42 NF1 patients and in 22 healthy individuals. Linear regression analysis revealed an association between total internal tumor load and the number of subcutaneous tumors (i.e. tumors under the skin).
Serum levels were significantly higher in NF1 patients than in healthy controls. MIA serum levels were significantly higher in NF1 patients with plexiform neurofibromas and with high tumor load than in patients without such tumors. Notably, MIA serum levels correlated significantly with internal tumor burden. The data indicate that elevated MIA serum level may be indicative of an increased internal tumor load.
Since there was an observed association between total internal tumor load and the number of plexiform tumors, a larger study will be necessary to reveal the relative contributions of internal, subcutaneous and possibly also cutaneous tumors to elevated MIA levels. Provided that the correlation can be confirmed in a larger cohort of NF1 patients, MIA could be a valuable biomarker for internal tumor load.
- Kolanczyk et al. MIA is a potential biomarker for tumor load in neurofibromatosis type 1. BMC Med. 2011 Jul 4;9(1):82. [Epub ahead of print]
- Kolanczyk et al. Multiple roles for neurofibromin in skeletal development and growth. Hum Mol Genet 2007, 16:874- 886.
- Elefteriou et al. ATF4 mediation of NF1 functions in osteoblast reveals a nutritional basis for congenital skeletal dysplasiae. Cell Metab 2006, 4:441-451.
- Miller et al. Integrative genomic analyses of neurofibromatosis tumours identify SOX9 as a biomarker and survival gene. EMBO Mol Med 2009, 1:236-248.