title: Evaluation of genes identified by microarray analysis in favorable neuroblastoma.
abstract: OBJECTIVE
  The biological heterogeneity of neuroblastoma results in a varied outcome ranging from spontaneous regression to fatal tumor progression. Microarray expression profiling and genetic polymorphism arrays may help identify key genes that differ in aggressive neuroblastomas from those observed in tumors associated with a favorable outcome.
  
  
  METHODS
  Total RNA was extracted from 16 neuroblastomas obtained from patients who subsequently died of the disease and from 16 favorable neuroblastomas and analyzed using a human whole genome oligomicroarray (55K CodeLink). Genes overexpressed in favorable tumors were subsequently analyzed in 121 neuroblastoma tumors obtained before chemotherapy using real-time RT-PCR. And among these cases, expression levels of these genes were also analyzed in 20 tumors obtained after chemotherapy.
  
  
  RESULTS
  Oligomicroarray analysis revealed the overexpression of 283 genes in favorable tumors that were associated with either regressing or maturing tumors. Three candidate genes, including DHRS3, NROB1, and CYP26A1, were selected that were significantly overexpressed in favorable tumors by quantitative real-time RT-PCR (P < 0.01). No cases with overexpression of all three genes showed poor outcomes. In 20 post-chemotherapeutic tumors, the expression levels of these genes increased in the cases where patients survived but decreased in the fatal cases.
  
  
  CONCLUSIONS
  Using microarray expression profiling, we identified genes that exhibit altered gene expression in neuroblastoma tumors associated with a favorable outcome. These candidates warrant further study for use in risk assessment and/or as therapeutic targets in neuroblastoma.
authors.affiliation: Department of Pediatric Surgery, Graduate School of Biomedical Science, Natural Center for Basic Research and Development, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima, 734-8551, Japan. nkamei@hiroshima-u.ac.jp
authors.forename: Naomi
authors.initials: N
authors.lastname: Kamei
authors.forename: Keiko
authors.initials: K
authors.lastname: Hiyama
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Yamaoka
authors.forename: Arata
authors.initials: A
authors.lastname: Kamimatsuse
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Onitake
authors.forename: Taijiro
authors.initials: T
authors.lastname: Sueda
authors.forename: Eiso
authors.initials: E
authors.lastname: Hiyama
mesh_terms: D002648:Child; D002675:Child, Preschool; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D009447:Neuroblastoma / Q000145:classification / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis
references.citation: Cancer Lett. 2002 Oct 28;184(2):127-47
references.pmid: 12127685
references.citation: Cancer. 1990 Nov 1;66(9):1879-87
references.pmid: 2224784
references.citation: J Clin Oncol. 1988 Dec;6(12):1874-81
references.pmid: 3199170
references.citation: Genes Chromosomes Cancer. 2004 Jun;40(2):120-32
references.pmid: 15101045
references.citation: Mol Cancer Ther. 2006 Mar;5(3):767-75
references.pmid: 16546992
references.citation: Nat Genet. 2002 May;31(1):84-8
references.pmid: 11953746
references.citation: Development. 2003 Apr;130(7):1449-59
references.pmid: 12588859
references.citation: Birth Defects Res A Clin Mol Teratol. 2006 Feb;76(2):86-95
references.pmid: 16463413
references.citation: Int J Oncol. 2005 Jul;27(1):87-95
references.pmid: 15942647
references.citation: J Pediatr Surg. 2003 Dec;38(12):1730-4
references.pmid: 14666454
references.citation: Nat Rev Cancer. 2003 Mar;3(3):203-16
references.pmid: 12612655
references.citation: Pediatr Surg Int. 2004 Jan;20(1):33-8
references.pmid: 14691637
references.citation: Cancer. 1999 Jul 15;86(2):364-72
references.pmid: 10421273