title: Comprehensive genetic and histopathologic study reveals three types of neuroblastoma tumors.
abstract: OBJECTIVE
  To determine the relationship between multiple genetic features, tumor morphology, and prognosis in neuroblastoma.
  
  
  METHODS
  The genetic alterations and morphologic features that underpin three histopathologic risk classifications were analyzed in 108 neuroblastoma patients. Tumors were subdivided into four groups based on the three most frequent and prognostically significant genetic alterations (17q gain, 1p deletion, and MYCN amplification), and all other genetic, morphologic, and clinical data were analyzed with respect to these groups.
  
  
  RESULTS
  Our analyses identify three nonoverlapping tumor types with distinct genetic and morphologic features, defined here as types 1, 2, and 3. Type 1 tumors show none of the three significant genetic alterations and have good prognosis. Both type 2 (17q gain only or 17q gain and 1p del) and type 3 (17q gain, 1p del, and MYCN amplification) tumors progress. However, these tumor types are distinguished clinically by having significantly different median age at diagnosis and median progression-free survival (PFS). Multivariate analysis indicates that 17q gain is the only independent prognostic factor among all genetic, histopathologic, and clinical factors analyzed. Among histopathologic risk systems, the International Neuroblastoma Pathology Classification was the best predictor of PFS.
  
  
  CONCLUSIONS
  Our results indicate that specific combinations of genetic changes in neuroblastoma tumors contribute to distinct morphologic and clinical features. Furthermore, the identification of two genetically and morphologically distinct types of progressing tumors suggests that possibilities for different therapeutic regimens should be investigated.
authors.affiliation: Human Genetics Unit, School of Biochemistry and Genetics, University of Newcastle upon Tyne, United Kingdom. M.A.Lastowska@ncl.ac.uk
authors.forename: M
authors.initials: M
authors.lastname: Lastowska
authors.forename: C
authors.initials: C
authors.lastname: Cullinane
authors.forename: S
authors.initials: S
authors.lastname: Variend
authors.forename: S
authors.initials: S
authors.lastname: Cotterill
authors.forename: N
authors.initials: N
authors.lastname: Bown
authors.forename: S
authors.initials: S
authors.lastname: O'Neill
authors.forename: K
authors.initials: K
authors.lastname: Mazzocco
authors.forename: P
authors.initials: P
authors.lastname: Roberts
authors.forename: J
authors.initials: J
authors.lastname: Nicholson
authors.forename: C
authors.initials: C
authors.lastname: Ellershaw
authors.forename: A D
authors.initials: AD
authors.lastname: Pearson
authors.forename: M S
authors.initials: MS
authors.lastname: Jackson
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D018572:Disease-Free Survival; D005784:Gene Amplification; D016259:Genes, myc / Q000235:genetics; D005819:Genetic Markers; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D007223:Infant; D007494:Ireland / Q000453:epidemiology; D015999:Multivariate Analysis; D009154:Mutation; D009447:Neuroblastoma / Q000235:genetics* / Q000473:pathology*; D011379:Prognosis; D016016:Proportional Hazards Models; D018709:Statistics, Nonparametric; D015996:Survival Rate; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D005819:Genetic Markers; D018960:Hyaluronan Receptors