title: MIA is a potential biomarker for tumour load in neurofibromatosis type 1.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Institute of Medical Genetics, Charité, Universitätsmedizin Berlin, Humboldt University, Augustenburger Platz 1, D-13353 Berlin, Germany. kolanshy@molgen.mpg.de
authors: Mateusz
authors: M
authors: Kolanczyk
authors: Victor
authors: V
authors: Mautner
authors: Nadine
authors: N
authors: Kossler
authors: Rosa
authors: R
authors: Nguyen
authors: Jirko
authors: J
authors: Kühnisch
authors: Tomasz
authors: T
authors: Zemojtel
authors: Aleksander
authors: A
authors: Jamsheer
authors: Eike
authors: E
authors: Wegener
authors: Boris
authors: B
authors: Thurisch
authors: Sigrid
authors: S
authors: Tinschert
authors: Nikola
authors: N
authors: Holtkamp
authors: Su-Jin
authors: SJ
authors: Park
authors: Patricia
authors: P
authors: Birch
authors: David
authors: D
authors: Kendler
authors: Anja
authors: A
authors: Harder
authors: Stefan
authors: S
authors: Mundlos
authors: Lan
authors: L
authors: Kluwe
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis*; D004195:Disease Models, Animal; D016326:Extracellular Matrix Proteins / Q000032:analysis*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis*; D009456:Neurofibromatosis 1 / Q000473:pathology*; D047368:Tumor Burden; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D016326:Extracellular Matrix Proteins; C090059:MIA protein, human; C513263:Mia protein, mouse; D009363:Neoplasm Proteins