title: IGF2BP1 harbors prognostic significance by gene gain and diverse expression in neuroblastoma.
abstract: OBJECTIVE
  Chromosomal 17q21-ter gain in neuroblastoma is both a common and prognostically significant event. The insulin-like growth factor-2 mRNA-binding protein 1 (IGF2BP1) gene is located near the proximal edge of this region. Here, its prognostic value is evaluated in neuroblastoma.
  
  
  METHODS
  The mRNA expression of IGF2BP family members was first evaluated by microarray data sets. In addition, in a separate cohort of 69 tumors, IGF2BP1 gene copy number, mRNA, and protein abundance were determined and compared with clinical parameters.
  
  
  RESULTS
  In two independent microarray data sets, 77% to 100% of tumors had substantial IGF2BP1 mRNA levels measured. High IGF2BP1 transcript abundance was significantly associated with stage 4 tumors (P < .001) and decreased patient survival (P < .001). IGF2BP1 was also associated with MYCN gene amplification and MYCN mRNA abundance. In the 69 neuroblastoma samples, IGF2BP1 DNA copy number (increased in 84% of tumors), mRNA, and protein abundance were significantly higher in stage 4 compared with stage 1 tumors. Importantly, IGF2BP1 protein levels were associated with lower overall patient survival (P = .012) and positively correlated with MYCN mRNA, even when excluding MYCN-amplified tumors. Moreover, IGF2BP1 clearly affected MYCN expression and neuroblastoma cell survival in vitro.
  
  
  CONCLUSIONS
  In neuroblastoma, IGF2BP1 was expressed in the majority of neuroblastoma specimens analyzed and was associated with lower overall patient survival and MYCN abundance. These data demonstrate that IGF2BP1 is a potential oncogene and an independent negative prognostic factor in neuroblastoma.
authors.affiliation: Jessica L. Bell, Raseswari Turlapati, and Stefan Hüttelmaier, Martin Luther University Halle-Wittenberg, Halle; Johannes H. Schulte, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, and University Children's Hospital Essen, Essen; Johannes H. Schulte, German Cancer Consortium and German Cancer Research Center, Heidelberg, Germany; and Tao Liu, Children's Cancer Institute Australia for Medical Research and University of New South Wales, Randwick, New South Wales, Australia.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Bell
authors.affiliation: Jessica L. Bell, Raseswari Turlapati, and Stefan Hüttelmaier, Martin Luther University Halle-Wittenberg, Halle; Johannes H. Schulte, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, and University Children's Hospital Essen, Essen; Johannes H. Schulte, German Cancer Consortium and German Cancer Research Center, Heidelberg, Germany; and Tao Liu, Children's Cancer Institute Australia for Medical Research and University of New South Wales, Randwick, New South Wales, Australia.
authors.forename: Raseswari
authors.initials: R
authors.lastname: Turlapati
authors.affiliation: Jessica L. Bell, Raseswari Turlapati, and Stefan Hüttelmaier, Martin Luther University Halle-Wittenberg, Halle; Johannes H. Schulte, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, and University Children's Hospital Essen, Essen; Johannes H. Schulte, German Cancer Consortium and German Cancer Research Center, Heidelberg, Germany; and Tao Liu, Children's Cancer Institute Australia for Medical Research and University of New South Wales, Randwick, New South Wales, Australia.
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.affiliation: Jessica L. Bell, Raseswari Turlapati, and Stefan Hüttelmaier, Martin Luther University Halle-Wittenberg, Halle; Johannes H. Schulte, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, and University Children's Hospital Essen, Essen; Johannes H. Schulte, German Cancer Consortium and German Cancer Research Center, Heidelberg, Germany; and Tao Liu, Children's Cancer Institute Australia for Medical Research and University of New South Wales, Randwick, New South Wales, Australia.
authors.forename: Johannes H
authors.initials: JH
authors.lastname: Schulte
authors.affiliation: Jessica L. Bell, Raseswari Turlapati, and Stefan Hüttelmaier, Martin Luther University Halle-Wittenberg, Halle; Johannes H. Schulte, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, and University Children's Hospital Essen, Essen; Johannes H. Schulte, German Cancer Consortium and German Cancer Research Center, Heidelberg, Germany; and Tao Liu, Children's Cancer Institute Australia for Medical Research and University of New South Wales, Randwick, New South Wales, Australia. stefan.huettelmaier@medizin.uni-halle.de.
authors.forename: Stefan
authors.initials: S
authors.lastname: Hüttelmaier
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D030541:Databases, Genetic; D018572:Disease-Free Survival; D005784:Gene Amplification; D018628:Gene Dosage; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D000071447:N-Myc Proto-Oncogene Protein; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000628:therapy; D009687:Nuclear Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D015513:Oncogene Proteins / Q000235:genetics; D010641:Phenotype; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000032:analysis; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D012307:Risk Factors; D013997:Time Factors; D014162:Transfection; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; C406144:IGF2BP1 protein, human; C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins