Role of ploidy, chromosome 1p, and Schwann cells in the maturation of neuroblastoma

N Engl J Med. 1996 Jun 6;334(23):1505-11. doi: 10.1056/NEJM199606063342304.

Abstract

Background: Neuroblastoma is a heterogeneous disease, with manifestations ranging from spontaneous regression to lethal spread. Sometimes the tumor spontaneously differentiates toward a benign ganglioneuroma (maturing neuroblastoma). The prognosis is frequently related to ploidy, deletions in the short arm of chromosome 1, and amplifications of the N-myc oncogene. Maturing neuroblastomas consist of both neuronal cells and Schwann cells. We investigated the genetic composition of both cell types in maturing neuroblastomas, to determine the relation between genetic abnormalities and maturation.

Methods: We studied 20 maturing and mature neuroblastomas by in situ hybridization to count the chromosomes and evaluate possible deletions in the short arm of chromosome 1 in neuronal and Schwann cells. The DNA content of the cells was measured by flow cytometry.

Results: Neuroblastic and ganglionic cells showed aberrations in the number of chromosomes. In situ hybridization and flow cytometry demonstrated near-trip-loidy in 18 of 19 tumors and pentaploidy in the remaining tumor. The Schwann cells in all 20 neuroblastomas contained normal numbers of chromosomes. In 18 tumors studied, there were no chromosome 1 deletions in either type of cell.

Conclusions: The Schwann cells in maturing neuroblastomas differ genetically from the neuronal cells. The normal number of chromosomes in Schwann cells and the abnormal number in neuroblastic ganglionic cells suggests that Schwann cells are a reactive population of normal cells that invade the neuroblastoma. Near-trip-loidy of neuroblastoma cells and intact chromosome 1 are presumably genetic prerequisites for spontaneous organoid maturation, because we found no diploidy or chromosome 1 depletions in the neuronal cells of spontaneously maturing neuroblastomas.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child
  • Child, Preschool
  • Chromosome Deletion
  • Chromosomes, Human, Pair 1*
  • DNA, Neoplasm / analysis
  • Female
  • Flow Cytometry
  • Ganglia / chemistry
  • Ganglia / cytology
  • Humans
  • In Situ Hybridization
  • Infant
  • Male
  • Neuroblastoma / genetics*
  • Neuroblastoma / pathology
  • Ploidies*
  • Schwann Cells* / chemistry
  • Schwann Cells* / cytology

Substances

  • DNA, Neoplasm