Open Access Open Badges Research article

MIA is a potential biomarker for tumour load in neurofibromatosis type 1

Mateusz Kolanczyk12*, Victor Mautner3, Nadine Kossler12, Rosa Nguyen3, Jirko Kühnisch2, Tomasz Zemojtel4, Aleksander Jamsheer56, Eike Wegener12, Boris Thurisch12, Sigrid Tinschert7, Nikola Holtkamp89, Su-Jin Park9, Patricia Birch10, David Kendler11, Anja Harder12, Stefan Mundlos129 and Lan Kluwe133

Author affiliations

1 Institute of Medical Genetics, Charité, Universitätsmedizin Berlin, Humboldt University, Augustenburger Platz 1, D-13353 Berlin, Germany

2 Development and Disease Group, Max Planck Institute for Molecular Genetics, Ihnestrasse 63-73, D-14195 Berlin, Germany

3 Department of Oral and Maxillofacial Surgery, Department of Neurology, University Hospital Hamburg-Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany

4 Department of Computational Molecular Biology, Max Planck Institute for Molecular Genetics, Ihnestrasse 63-73, D-14195 Berlin, Germany

5 Center for Medical Genetics in Poznań, ul. Grudzieniec 4, 60-601 Poznań, Poland

6 Department of Medical Genetics, Medical University of Poznan, 60-352 Poznań, Poland

7 Institut für Klinische Genetik, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Fetscherstrasse 74, 01307 Dresden, Germany

8 Institute of Neuropathology, Charité-Universitätsmedizin Berlin, CVK, Augustenburger Platz 1, D-13353 Berlin, Germany

9 Berlin Center for Regenerative Therapies, Charité-Universitätsmedizin Berlin Augustenburger Platz 1, D-13353 Berlin, Germany

10 Department of Medical Genetics, University of British Columbia, Box 153, 4500 Oak Street, Vancouver, BC V6H 3N1, Canada

11 Faculty of Medicine, University of British Columbia 600 - 1285 West Broadway Vancouver, BC V6H 3X8, Canada

12 Institute of Neuropathology, University Hospital Münster, Domagkstrasse 19, D-48149 Münster, Germany

13 German Cancer Research Center, Im Neuenheimer Feld, D-69120 Heidelberg, Germany

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Citation and License

BMC Medicine 2011, 9:82  doi:10.1186/1741-7015-9-82

Published: 4 July 2011



Neurofibromatosis type 1 (NF1) is a frequent genetic disease characterized by multiple benign tumours with increased risk for malignancy. There is currently no biomarker for tumour load in NF1 patients.


In situ hybridization and quantitative real-time polymerase reaction were applied to investigate expression of cartilage-specific genes in mice bearing conditional inactivation of NF1 in the developing limbs. These mice do not develop tumours but recapitulate aspects of NF1 bone dysplasia, including deregulation of cartilage differentiation. It has been recently shown that NF1 tumours require for their growth the master regulator of cartilage differentiation SOX9. We thus hypothesized that some of the cartilage-specific genes deregulated in an Nf1Prx1 mouse model might prove to be relevant biomarkers of NF1 tumours. We tested this hypothesis by analyzing expression of the SOX9 target gene product melanoma-inhibitory activity/cd-rap (MIA) in tumour and serum samples of NF1 patients.


Increased expression of Mia was found in Nf1-deficient cartilage in mice. In humans, MIA was expressed in all NF1-related tumours and its serum levels were significantly higher in NF1 patients than in healthy controls. Among NF1 patients, MIA serum levels were significantly higher in those with plexiform neurofibromas and in those with large number of cutaneous (> 1,000) or subcutaneous (> 100) neurofibromas than in patients without such tumours. Most notably, MIA serum levels correlated significantly with internal tumour burden.


MIA is a potential serum biomarker of tumour load in NF1 patients which could be useful in following the disease course and monitoring the efficacy of therapies.