Stepwise accumulation of distinct genomic aberrations in a patient with progressively metastasizing ependymoma

Genes Chromosomes Cancer. 2009 Mar;48(3):229-38. doi: 10.1002/gcc.20635.


Nonresectable ependymomas are associated with poor prognosis despite intensive radiochemotherapy and radiation. The molecular pathogenesis of ependymoma initiation and progression is largely unknown. We here present a case of therapy-refractory, progressive ependymoma with cerebrospinal as well as extraneural metastases, which allowed us for the first time to follow the stepwise accumulation of chromosome aberrations during disease progression. Genome-wide DNA copy-number analysis showed sequential deletions on chromosomes 1, 9, and 14 as well as a homozygous deletion of the CDKN2A locus, underscoring its role in tumor progression. Gradual loss at 1p36 was associated with loss of protein expression of the putative tumor suppressor gene AJAP1/SHREW1. In summary, this is the first report on acquired genomic aberrations in ependymoma over time pointing to novel candidate tumor suppressor genes. This analysis provides molecular insights into the chronology of genetic events in this case from initial localized tumor to widespread metastasized disease.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / pathology
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism
  • Chromosome Deletion*
  • Chromosomes, Human, Pair 1 / genetics
  • Chromosomes, Human, Pair 14 / genetics
  • Chromosomes, Human, Pair 9 / genetics
  • Ependymoma / genetics*
  • Ependymoma / pathology
  • Ependymoma / secondary
  • Fatal Outcome
  • Female
  • Gene Expression
  • Genes, Tumor Suppressor
  • Humans
  • Microarray Analysis
  • Peritoneal Neoplasms / pathology
  • Peritoneal Neoplasms / secondary
  • Spinal Neoplasms / pathology
  • Spinal Neoplasms / secondary
  • Tumor Cells, Cultured


  • AJAP1 protein, human
  • Cell Adhesion Molecules