Medulloblastoma subgroups remain stable across primary and metastatic compartments

Xin Wang, Adrian M. Dubuc, Vijay Ramaswamy, Stephen Mack, Deena M.A. Gendoo, Marc Remke, Xiaochong Wu, Livia Garzia, Betty Luu, Florence Cavalli, John Peacock, Borja López, Patryk Skowron, David Zagzag, David Lyden, Caitlin Hoffman, Yoon Jae Cho, Charles Eberhart, Tobey MacDonald, Xiao Nan LiTimothy Van Meter, Paul A. Northcott, Benjamin Haibe-Kains, Cynthia Hawkins, James T. Rutka, Eric Bouffet, Stefan M. Pfister, Andrey Korshunov, Michael D. Taylor

Research output: Contribution to journalArticlepeer-review

74 Scopus citations


Medulloblastoma comprises four distinct molecular variants with distinct genetics, transcriptomes, and outcomes. Subgroup affiliation has been previously shown to remain stable at the time of recurrence, which likely reflects their distinct cells of origin. However, a therapeutically relevant question that remains unanswered is subgroup stability in the metastatic compartment. We assembled a cohort of 12-paired primary-metastatic tumors collected in the MAGIC consortium, and established their molecular subgroup affiliation by performing integrative gene expression and DNA methylation analysis. Frozen tissues were collected and profiled using Affymetrix gene expression arrays and Illumina methylation arrays. Class prediction and hierarchical clustering were performed using existing published datasets. Our molecular analysis, using consensus integrative genomic data, establishes the unequivocal maintenance of molecular subgroup affiliation in metastatic medulloblastoma. We further validated these findings by interrogating a non-overlapping cohort of 19 pairs of primary-metastatic tumors from the Burdenko Neurosurgical Institute using an orthogonal technique of immunohistochemical staining. This investigation represents the largest reported primary-metastatic paired cohort profiled to date and provides a unique opportunity to evaluate subgroup-specific molecular aberrations within the metastatic compartment. Our findings further support the hypothesis that medulloblastoma subgroups arise from distinct cells of origin, which are carried forward from ontogeny to oncology.

Original languageEnglish (US)
Pages (from-to)449-457
Number of pages9
JournalActa Neuropathologica
Issue number3
StatePublished - Feb 18 2015
Externally publishedYes


  • DNA methylation
  • Gene expression
  • Integrative genomics
  • Medulloblastoma
  • Metastasis
  • Molecular subgroups

ASJC Scopus subject areas

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


Dive into the research topics of 'Medulloblastoma subgroups remain stable across primary and metastatic compartments'. Together they form a unique fingerprint.

Cite this