title: Intratumoural heterogeneity of 1p deletions and MYCN amplification in neuroblastomas.
abstract: BACKGROUND
  At least three genetic hallmarks identify aggressive tumour behaviour in neuroblastomas; amplification of the oncogene MYCN; deletion (loss of heterozygosity [LOH]) at the short arm of chromosome 1 (del1p36), seen in approximately 28% of the cases; and di-tetraploidy. The MYCN oncogene is amplified in approximately 23% of all neuroblastomas and becomes important for the stratification of therapy in localised and 4s tumours. Up to now, it has been believed that the genetic constellation of neuroblastic tumours is stable and does not alter during tumour evolution or during tumour progression.
  
  
  METHODS
  Using fluorescence in situ hybridisation techniques (FISH) to investigate different tumour areas on touch preparations and histological sections, we show that genetic heterogeneity can be detected in neuroblastomas, especially in tumours detected by urinary mass screening.
  
  
  CONCLUSIONS
  The identification of such cell clones is important, because the MYCN amplification and/or the deletion at 1p36 appear to be responsible for aggressive local growth and development of metastases.
authors.affiliation: CCRI, Children's Cancer Research Institute, St Anna Kinderspital, Vienna, Austria. ambros@ccri.univie.ac.at
authors.forename: P F
authors.initials: PF
authors.lastname: Ambros
authors.forename: I M
authors.initials: IM
authors.lastname: Ambros
authors.forename: R
authors.initials: R
authors.lastname: Kerbl
authors.forename: A
authors.initials: A
authors.lastname: Luegmayr
authors.forename: S
authors.initials: S
authors.lastname: Rumpler
authors.forename: R
authors.initials: R
authors.lastname: Ladenstein
authors.forename: G
authors.initials: G
authors.lastname: Amann
authors.forename: H
authors.initials: H
authors.lastname: Kovar
authors.forename: E
authors.initials: E
authors.lastname: Horcher
authors.forename: B
authors.initials: B
authors.lastname: De Bernardi
authors.forename: J
authors.initials: J
authors.lastname: Michon
authors.forename: H
authors.initials: H
authors.lastname: Gadner
mesh_terms: D002878:Chromosomes, Human, Pair 1 / Q000235:genetics* / Q000648:ultrastructure; D002999:Clone Cells / Q000648:ultrastructure; D018450:Disease Progression; D005784:Gene Amplification; D016259:Genes, myc; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D019656:Loss of Heterozygosity; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D014411:Neoplastic Stem Cells / Q000648:ultrastructure; D009447:Neuroblastoma / Q000235:genetics* / Q000473:pathology; D011379:Prognosis