title: Chromosome 1p and 11q deletions and outcome in neuroblastoma.
abstract: BACKGROUND
  Neuroblastoma is a childhood cancer with considerable morbidity and mortality. Tumor-derived biomarkers may improve risk stratification.
  
  
  METHODS
  We screened 915 samples of neuroblastoma for loss of heterozygosity (LOH) at chromosome bands 1p36 and 11q23. Additional analyses identified a subgroup of cases of 11q23 LOH with unbalanced 11q LOH (unb11q LOH; defined as loss of 11q with retention of 11p). The associations of LOH with relapse and survival were determined.
  
  
  RESULTS
  LOH at 1p36 was identified in 209 of 898 tumors (23 percent) and LOH at 11q23 in 307 of 913 (34 percent). Unb11q LOH was found in 151 of 307 tumors with 11q23 LOH (17 percent of the total cohort). There was a strong association of 1p36 LOH, 11q23 LOH, and unb11q LOH with most high-risk disease features (P<0.001). LOH at 1p36 was associated with amplification of the MYCN oncogene (P<0.001), but 11q23 LOH and unb11q LOH were not (P<0.001 and P=0.002, respectively). Cases with unb11q LOH were associated with three-year event-free and overall survival rates (+/-SE) of 50+/-5 percent and 66+/-5 percent, respectively, as compared with 74+/-2 percent and 83+/-2 percent among cases without unb11q LOH (P<0.001 for both comparisons). In a multivariate model, unb11q LOH was independently associated with decreased event-free survival (P=0.009) in the entire cohort, and both 1p36 LOH and unb11q LOH were independently associated with decreased progression-free survival in the subgroup of patients with features of low-risk and intermediate-risk disease (P=0.002 and P=0.02, respectively).
  
  
  CONCLUSIONS
  Unb11q LOH and 1p36 LOH are independently associated with a worse outcome in patients with neuroblastoma.
authors.affiliation: Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, PA 19104-4318, USA.
authors.forename: Edward F
authors.initials: EF
authors.lastname: Attiyeh
authors.forename: Wendy B
authors.initials: WB
authors.lastname: London
authors.forename: Yael P
authors.initials: YP
authors.lastname: Mossé
authors.forename: Qun
authors.initials: Q
authors.lastname: Wang
authors.forename: Cynthia
authors.initials: C
authors.lastname: Winter
authors.forename: Deepa
authors.initials: D
authors.lastname: Khazi
authors.forename: Patrick W
authors.initials: PW
authors.lastname: McGrady
authors.forename: Robert C
authors.initials: RC
authors.lastname: Seeger
authors.forename: A Thomas
authors.initials: AT
authors.lastname: Look
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Shimada
authors.forename: Garrett M
authors.initials: GM
authors.lastname: Brodeur
authors.forename: Susan L
authors.initials: SL
authors.lastname: Cohn
authors.forename: Katherine K
authors.initials: KK
authors.lastname: Matthay
authors.forename: John M
authors.initials: JM
authors.lastname: Maris
mesh_terms: D000704:Analysis of Variance; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D018572:Disease-Free Survival; D005500:Follow-Up Studies; D005784:Gene Amplification; D005819:Genetic Markers; D006801:Humans; D007223:Infant; D019656:Loss of Heterozygosity; D000071447:N-Myc Proto-Oncogene Protein; D009447:Neuroblastoma / Q000235:genetics* / Q000401:mortality; D009687:Nuclear Proteins / Q000235:genetics*; D015513:Oncogene Proteins / Q000235:genetics*; D016016:Proportional Hazards Models; D012307:Risk Factors; D016019:Survival Analysis
chemical_list: D005819:Genetic Markers; C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins