Genetic instability and intratumoral heterogeneity in neuroblastoma with MYCN amplification plus 11q deletion

PLoS One. 2013;8(1):e53740. doi: 10.1371/journal.pone.0053740. Epub 2013 Jan 14.

Abstract

Background/aim: Genetic analysis in neuroblastoma has identified the profound influence of MYCN amplification and 11q deletion in patients' prognosis. These two features of high-risk neuroblastoma usually occur as mutually exclusive genetic markers, although in rare cases both are present in the same tumor. The purpose of this study was to characterize the genetic profile of these uncommon neuroblastomas harboring both these high-risk features.

Methods: We selected 18 neuroblastomas with MNA plus 11q loss detected by FISH. Chromosomal aberrations were analyzed using Multiplex Ligation-dependent Probe Amplification and Single Nucleotide Polymorphism array techniques.

Results and conclusion: This group of tumors has approximately the same high frequency of aberrations as found earlier for 11q deleted tumors. In some cases, DNA instability generates genetic heterogeneity, and must be taken into account in routine genetic diagnosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child
  • Child, Preschool
  • Chromosome Breakpoints
  • Chromosome Deletion*
  • Chromosomes, Human, Pair 11 / genetics*
  • Female
  • Gene Amplification*
  • Genetic Markers / genetics
  • Genetic Predisposition to Disease / genetics
  • Humans
  • Infant
  • Male
  • N-Myc Proto-Oncogene Protein
  • Neuroblastoma / genetics*
  • Neuroblastoma / pathology*
  • Nuclear Proteins / genetics*
  • Oncogene Proteins / genetics*
  • Polymorphism, Single Nucleotide

Substances

  • Genetic Markers
  • MYCN protein, human
  • N-Myc Proto-Oncogene Protein
  • Nuclear Proteins
  • Oncogene Proteins

Grants and funding

This study was supported by the grants: RD06/0020/0102 and PI10/0015 (ISCIII & ERDF); 396/2009 (FAECC); 09/1217 (Swedish Cancer Society); and 08/098 (Children’s Cancer Foundation). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.