title: Chromosomal and microRNA expression patterns reveal biologically distinct subgroups of 11q- neuroblastoma.
abstract: OBJECTIVE
  The purpose of this study was to further define the biology of the 11q- neuroblastoma tumor subgroup by the integration of array-based comparative genomic hybridization with microRNA (miRNA) expression profiling data to determine if improved patient stratification is possible.
  
  
  METHODS
  A set of primary neuroblastoma (n = 160), which was broadly representative of all genetic subtypes, was analyzed by array-based comparative genomic hybridization and for the expression of 430 miRNAs. A 15-miRNA expression signature previously shown to be predictive of clinical outcome was used to analyze an independent cohort of 11q- tumors (n = 37).
  
  
  RESULTS
  Loss of 4p and gain of 7q occurred at a significantly higher frequency in the 11q- tumors, further defining the genetic characteristics of this subtype. The 11q- tumors could be split into two subgroups using a miRNA expression survival signature that differed significantly in clinical outcome and the overall frequency of large-scale genomic imbalances, with the poor survival subgroup having significantly more imbalances. miRNAs from the expression signature, which were upregulated in unfavorable tumors, were predicted to target downregulated genes from a published mRNA expression classifier of clinical outcome at a higher-than-expected frequency, indicating the miRNAs might contribute to the regulation of genes within the signature.
  
  
  CONCLUSIONS
  We show that two distinct biological subtypes of neuroblastoma with loss of 11q occur, which differ in their miRNA expression profiles, frequency of segmental imbalances, and clinical outcome. A miRNA expression signature, combined with an analysis of segmental imbalances, provides greater prediction of event-free survival and overall survival outcomes than 11q status by itself, improving patient stratification.
authors.affiliation: Department of Cancer Genetics, Royal College of Surgeons in Ireland, Dublin, Ireland.
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Buckley
authors.forename: Leah
authors.initials: L
authors.lastname: Alcock
authors.forename: Kenneth
authors.initials: K
authors.lastname: Bryan
authors.forename: Isabella
authors.initials: I
authors.lastname: Bray
authors.forename: Johannes H
authors.initials: JH
authors.lastname: Schulte
authors.forename: Alexander
authors.initials: A
authors.lastname: Schramm
authors.forename: Angelika
authors.initials: A
authors.lastname: Eggert
authors.forename: Pieter
authors.initials: P
authors.lastname: Mestdagh
authors.forename: Katleen
authors.initials: K
authors.lastname: De Preter
authors.forename: Jo
authors.initials: J
authors.lastname: Vandesompele
authors.forename: Frank
authors.initials: F
authors.lastname: Speleman
authors.forename: Raymond L
authors.initials: RL
authors.lastname: Stallings
mesh_terms: D002872:Chromosome Deletion; D002880:Chromosomes, Human, Pair 11; D018572:Disease-Free Survival; D018628:Gene Dosage; D020869:Gene Expression Profiling; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D009447:Neuroblastoma / Q000145:classification / Q000235:genetics*
chemical_list: D035683:MicroRNAs
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