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

Item Type:Article
Title:Stepwise accumulation of distinct genomic aberrations in a patient with progressively metastasizing ependymoma
Creators Name:Milde, T., Pfister, S., Korshunov, K., Deubzer, H.E., Oehme, I., Ernst, A., Starzinski-Powitz, A., Seitz, A., Lichter, P., von Deimling, A. and Witt, O.
Abstract: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.
Keywords:Adolescent, Brain Neoplasms, Cell Adhesion Molecules, Chromosome Deletion, Cultured Tumor Cells, Ependymoma, Fatal Outcome, Gene Expression, Human Chromosomes Pair 1, Human Chromosomes Pair 9, Human Chromosomes Pair 14, Microarray Analysis, Peritoneal Neoplasms, Spinal Neoplasms, Tumor Suppressor Genes
Source:Genes Chromosomes & Cancer
Page Range:229-238
Date:March 2009
Official Publication:https://doi.org/10.1002/gcc.20635
PubMed:View item in PubMed

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