title: Clinical significance of NTRK family gene expression in neuroblastomas.
abstract: BACKGROUND
  Neuroblastomas (NBs) are characterized by clinical heterogeneity, from spontaneous regression to relentless progression. The pattern of NTRK family gene expression contributes to these disparate behaviors. TrkA/NTRK1 is expressed in favorable NBs that regress or differentiate, whereas TrkB/NTRK2 and its ligand brain-derived neurotrophic factor (BDNF) are co-expressed in unfavorable NBs, representing an autocrine survival pathway. We determined the significance of NTRK family gene expression in a large, representative set of primary NBs.
  
  
  METHODS
  We analyzed the expression of the following genes in 814 NBs using quantitative real-time reverse transcriptase polymerase chain reaction (RT-PCR): NTRK1, NTRK2, NTRK3, P75/NGFR, nerve growth factor (NGF), BDNF, IGFR1, and EGFR. Expression (high vs. low) was dichotomized by median expression value and compared to clinical and biological variables as well as outcome.
  
  
  RESULTS
  High NTRK1 expression was strongly correlated with favorable age, stage, MYCN status, histology, ploidy, risk group, and outcome (P < 0.0001 for all). However, it did not add significantly to the panel of prognostic variables currently used for cooperative group trials. NTRK2 expression was associated with risk factors but not with outcome. High NGF expression was also associated with most risk factors and weakly with unfavorable outcome.
  
  
  CONCLUSIONS
  High expression of NTRK1 is strongly associated with favorable risk factors and outcome in a large, representative population of NB patients. It did not add significantly to the current risk prediction algorithm, but it may contribute to future expression classifiers. Indeed, prospective assessment of NTRK1 and NTRK2 expression will identify tumors that would be candidates for NTRK-targeted therapy, either alone or in combination with conventional agents.
authors: Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
authors: Jennifer E
authors: JE
authors: Light
authors: Hiroshi
authors: H
authors: Koyama
authors: Jane E
authors: JE
authors: Minturn
authors: Ruth
authors: R
authors: Ho
authors: Anisha M
authors: AM
authors: Simpson
authors: Radhika
authors: R
authors: Iyer
authors: Jennifer L
authors: JL
authors: Mangino
authors: Venkatadri
authors: V
authors: Kolla
authors: Wendy B
authors: WB
authors: London
authors: Garrett M
authors: GM
authors: Brodeur
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007223:Infant; D000071447:N-Myc Proto-Oncogene Protein; D009414:Nerve Growth Factors / Q000235:genetics* / Q000378:metabolism; D009447:Neuroblastoma / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D015513:Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D020800:Receptor, Nerve Growth Factor / Q000235:genetics* / Q000378:metabolism; D020917:Receptor, trkA / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009414:Nerve Growth Factors; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D012333:RNA, Messenger; D020800:Receptor, Nerve Growth Factor; D020917:Receptor, trkA