title: Relationship between MYCN copy number and expression in rhabdomyosarcomas and correlation with adverse prognosis in the alveolar subtype.
abstract: OBJECTIVE
  Amplification of the transcription factor MYCN is an important molecular diagnostic tool in stratifying treatment for neuroblastoma. Increased copy number and overexpression of MYCN in the pediatric cancer rhabdomyosarcoma has been described in a number of small studies with conflicting conclusions about its association with clinicopathologic characteristics. We aimed to study the phenomenon in the largest series to date.
  
  
  METHODS
  Using quantitative polymerase chain reaction, we measured MYCN copy number and expression levels in rhabdomyosarcoma samples from 113 and 92 individuals with a confirmed diagnosis of rhabdomyosarcoma, respectively.
  
  
  RESULTS
  Increased copy number of MYCN was found to be a feature of both the embryonal and alveolar subtypes. The copy number and expression levels were significantly greater in the alveolar subtype, although the range of expression in both subtypes spanned several orders of magnitude. MYCN copy number showed a significant correlation with expression in the alveolar subtype; this relationship between copy number and expression could be modeled as a logarithmic function. It is notable that relatively high expression frequently occurred in embryonal rhabdomyosarcoma without high copy number and that low expression was found in some cases with high copy number. In patients with alveolar rhabdomyosarcoma, overexpression (greater than median) or gain of genomic copies of MYCN were significantly associated with adverse outcome.
  
  
  CONCLUSIONS
  MYCN deregulation is a feature of rhabdomyosarcoma tumorigenesis, defines groups of patients with a poor prognosis, and is a potential target for novel therapies.
authors.affiliation: Molecular Cytogenetics, The Institute of Cancer Research, Sutton, Surrey, United Kingdom.
authors.forename: Daniel
authors.initials: D
authors.lastname: Williamson
authors.forename: Yong-Jie
authors.initials: YJ
authors.lastname: Lu
authors.forename: Tony
authors.initials: T
authors.lastname: Gordon
authors.forename: Raf
authors.initials: R
authors.lastname: Sciot
authors.forename: Anna
authors.initials: A
authors.lastname: Kelsey
authors.forename: Cyril
authors.initials: C
authors.lastname: Fisher
authors.forename: Christopher
authors.initials: C
authors.lastname: Poremba
authors.forename: John
authors.initials: J
authors.lastname: Anderson
authors.forename: Kathy
authors.initials: K
authors.lastname: Pritchard-Jones
authors.forename: Janet
authors.initials: J
authors.lastname: Shipley
mesh_terms: D002648:Child; D005260:Female; D018628:Gene Dosage; D016259:Genes, myc; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D011379:Prognosis; D012208:Rhabdomyosarcoma / Q000235:genetics* / Q000401:mortality