title: 17q gain in neuroblastoma predicts adverse clinical outcome. U.K. Cancer Cytogenetics Group and the U.K. Children's Cancer Study Group.
abstract: BACKGROUND
  It is now recognized that gain of chromosome 17 material is the most frequent genetic abnormality of neuroblastoma cells. Several studies have linked 17q gain with known adverse prognostic factors: patient age >1 year, advanced stage disease, deletion of chromosome arm 1 p, and amplification of the MYCN oncogene. We sought to further investigate the clinical and prognostic associations of chromosome 17 status in relation to other well-established predictive factors.
  
  
  METHODS
  In a collaborative study by UK cytogenetics centres, we compiled a series of 104 neuroblastoma tumours for which the status of chromosome 17 was confidently defined by cytogenetics, metaphase or interphase FISH, or CGH analysis. The results were correlated with data on 1p and MYCN, and with centrally collated clinical and survival information.
  
  
  RESULTS
  Gain of 17q (i.e., unbalanced gain of segment 17q21-qter) was found in 66.3% of tumours, while 33.7% showed a '17q normal' status (i.e., no gain at all, or gain of whole chromosome 17 relative to ploidy). Gain of 17q was strongly associated with advanced stage disease, patient age >1 year, 1p deletion, and MYCN amplification (all P< 0.01). In univariate analysis, 17q gain was a significant predictor of adverse outcome (projected 5 year relapse-free survival 15.6% compared to 75.2% in cases lacking this feature in tumour cells; (P < 0.0001). In multivariate analysis, 17q gain was more strongly associated with adverse outcome than was either stage (Stage 4 vs other combined) or 1p status.
  
  
  CONCLUSIONS
  We conclude that gain of chromosome segment 17q21-qter is of great biological and clinical importance in neuroblastoma, and that its detection at diagnosis should be a priority.
authors.affiliation: Department of Human Genetics, University of Newcastle upon Tyne, United Kingdom. Nicholas.bown@ncl.ac.uk
authors.forename: N
authors.initials: N
authors.lastname: Bown
authors.forename: M
authors.initials: M
authors.lastname: Lastowska
authors.forename: S
authors.initials: S
authors.lastname: Cotterill
authors.forename: S
authors.initials: S
authors.lastname: O'Neill
authors.forename: C
authors.initials: C
authors.lastname: Ellershaw
authors.forename: P
authors.initials: P
authors.lastname: Roberts
authors.forename: I
authors.initials: I
authors.lastname: Lewis
authors.forename: A D
authors.initials: AD
authors.lastname: Pearson
mesh_terms: D015139:Blotting, Southern; D002648:Child; D002675:Child, Preschool; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics / Q000648:ultrastructure; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics / Q000648:ultrastructure*; D015342:DNA Probes; D018572:Disease-Free Survival; D005500:Follow-Up Studies; D005784:Gene Amplification; D016259:Genes, myc; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007399:Interphase; D015993:Life Tables; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D009693:Nucleic Acid Hybridization; D011379:Prognosis; D012307:Risk Factors; D017384:Sequence Deletion; D016019:Survival Analysis; D014314:Trisomy; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D015342:DNA Probes