title: Prognostic significance of MDM2 gene expression in childhood neuroblastoma.
abstract: OBJECTIVE
  To investigate the association of MDM2 expression at the mRNA levels in neuroblastoma with clinical features and unfavorable disease factors to determine the possibility of it usage as a prognostic marker of neuroblastoma.
  
  
  METHODS
  Total RNA and DNA were extracted from tumor tissue samples of total 91 neuroblastoma patients (mean age: 39.45 ± 4.81 months). MDM2 mRNA levels were detected with Q-PCR. TP53 gene deletion was detected with FISH method. MYCN amplification was detected with -Q-PCR analysis in fresh tumor samples and FISH in FFPE samples.
  
  
  RESULTS
  We investigated the association of MDM2 mRNA expression with clinical outcome in neuroblastoma patients (n = 91). Kaplan - Meier curves showed a significant association of high MDM2 expression with poor event-free survival (p < 0.001). Clinical outcome of patients without MYCN amplification with low MDM2 expression was associated with better event-free survival than with high MDM2 expression (p < 0.001). Overexpression of MDM2 can be used as significant prognostic marker for patient stratification on risk groups and treatment optimization.
  
  
  CONCLUSIONS
  Our results showed that the high expression of MDM2 at mRNA levels is an important factor of neuroblastoma prognosis. It may be a valuable additional molecular marker in guiding specific therapy in MYCN non-amplified NB patients without TP53 gene deletion.
authors.affiliation: Laboratory of Experimental Oncology, National Cancer Institute, Kyiv 03022, Ukraine.
authors.forename: M V
authors.initials: MV
authors.lastname: Inomistova
authors.affiliation: Laboratory of Experimental Oncology, National Cancer Institute, Kyiv 03022, Ukraine.
authors.forename: N M
authors.initials: NM
authors.lastname: Svergun
authors.affiliation: Laboratory of Experimental Oncology, National Cancer Institute, Kyiv 03022, Ukraine.
authors.forename: N M
authors.initials: NM
authors.lastname: Khranovska
authors.affiliation: Laboratory of Experimental Oncology, National Cancer Institute, Kyiv 03022, Ukraine.
authors.forename: O V
authors.initials: OV
authors.lastname: Skachkova
authors.affiliation: Laboratory of Experimental Oncology, National Cancer Institute, Kyiv 03022, Ukraine.
authors.forename: O I
authors.initials: OI
authors.lastname: Gorbach
authors.affiliation: Pediatric Oncology Department, National Cancer Institute, Kyiv 03022, Ukraine.
authors.forename: G I
authors.initials: GI
authors.lastname: Klymnyuk
mesh_terms: D000293:Adolescent; D002648:Child; D018572:Disease-Free Survival; D015870:Gene Expression; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D053208:Kaplan-Meier Estimate; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D010524:Peripheral Nervous System Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics* / Q000378:metabolism; D012372:ROC Curve
chemical_list: C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2