A prognostic gene expression signature in infratentorial ependymoma

Khalida Wani, Terri S. Armstrong, Elizabeth Vera-Bolanos, Aditya Raghunathan, David Ellison, Richard Gilbertson, Brian Vaillant, Stewart Goldman, Roger J. Packer, Maryam Fouladi, Ian Pollack, Tom Mikkelsen, Michael Prados, Antonio Omuro, Riccardo Soffietti, Alicia Ledoux, Charmaine Wilson, Lihong Long, Mark R. Gilbert, Ken Aldape

Research output: Contribution to journalArticle

97 Scopus citations

Abstract

Patients with ependymoma exhibit a wide range of clinical outcomes that are currently unexplained by clinical or histological factors. Little is known regarding molecular biomarkers that could predict clinical behavior. Since recent data suggest that these tumors display biological characteristics according to their location (cerebral vs. infratentorial vs. spinal cord), rather than explore a broad spectrum of ependymoma, we focused on molecular alterations in ependymomas arising in the infratentorial compartment. Unsupervised clustering of available gene expression microarray data revealed two major subgroups of infratentorial ependymoma. Group 1 tumors over expressed genes that were associated with mesenchyme, Group 2 tumors showed no distinct gene ontologies. To assess the prognostic significance of these gene expression subgroups, real-time reverse transcriptase polymerase chain reaction assays were performed on genes defining the subgroups in a training set. This resulted in a 10-gene prognostic signature. Multivariate analysis showed that the 10-gene signature was an independent predictor of recurrence-free survival after adjusting for clinical factors. Evaluation of an external dataset describing subgroups of infratentorial ependymomas showed concordance of subgroup definition, including validation of the mesenchymal subclass. Importantly, the 10-gene signature was validated as a predictor of recurrence-free survival in this dataset. Taken together, the results indicate a link between clinical outcome and biologically identified subsets of infratentorial ependymoma and offer the potential for prognostic testing to estimate clinical aggressiveness in these tumors.

Original languageEnglish (US)
Pages (from-to)727-738
Number of pages12
JournalActa neuropathologica
Volume123
Issue number5
DOIs
StatePublished - May 1 2012

Keywords

  • Biomarker
  • Expression profiling
  • Gene expression signature
  • Infratentorial ependymoma
  • Microarray
  • Prognostic genes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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  • Cite this

    Wani, K., Armstrong, T. S., Vera-Bolanos, E., Raghunathan, A., Ellison, D., Gilbertson, R., Vaillant, B., Goldman, S., Packer, R. J., Fouladi, M., Pollack, I., Mikkelsen, T., Prados, M., Omuro, A., Soffietti, R., Ledoux, A., Wilson, C., Long, L., Gilbert, M. R., & Aldape, K. (2012). A prognostic gene expression signature in infratentorial ependymoma. Acta neuropathologica, 123(5), 727-738. https://doi.org/10.1007/s00401-012-0941-4