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 journalArticle

45 Citations (Scopus)

Abstract

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
Volume129
Issue number3
DOIs
StatePublished - Feb 18 2015
Externally publishedYes

Fingerprint

Medulloblastoma
Gene Expression
DNA Methylation
Transcriptome
Methylation
Cluster Analysis
Neoplasms
Maintenance
Staining and Labeling
Recurrence

Keywords

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

ASJC Scopus subject areas

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

Cite this

Wang, X., Dubuc, A. M., Ramaswamy, V., Mack, S., Gendoo, D. M. A., Remke, M., ... Taylor, M. D. (2015). Medulloblastoma subgroups remain stable across primary and metastatic compartments. Acta Neuropathologica, 129(3), 449-457. https://doi.org/10.1007/s00401-015-1389-0

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

In: Acta Neuropathologica, Vol. 129, No. 3, 18.02.2015, p. 449-457.

Research output: Contribution to journalArticle

Wang, X, Dubuc, AM, Ramaswamy, V, Mack, S, Gendoo, DMA, Remke, M, Wu, X, Garzia, L, Luu, B, Cavalli, F, Peacock, J, López, B, Skowron, P, Zagzag, D, Lyden, D, Hoffman, C, Cho, Y-J, Eberhart, C, MacDonald, T, Li, XN, Van Meter, T, Northcott, PA, Haibe-Kains, B, Hawkins, C, Rutka, JT, Bouffet, E, Pfister, SM, Korshunov, A & Taylor, MD 2015, 'Medulloblastoma subgroups remain stable across primary and metastatic compartments', Acta Neuropathologica, vol. 129, no. 3, pp. 449-457. https://doi.org/10.1007/s00401-015-1389-0
Wang X, Dubuc AM, Ramaswamy V, Mack S, Gendoo DMA, Remke M et al. Medulloblastoma subgroups remain stable across primary and metastatic compartments. Acta Neuropathologica. 2015 Feb 18;129(3):449-457. https://doi.org/10.1007/s00401-015-1389-0
Wang, Xin ; Dubuc, Adrian M. ; Ramaswamy, Vijay ; Mack, Stephen ; Gendoo, Deena M.A. ; Remke, Marc ; Wu, Xiaochong ; Garzia, Livia ; Luu, Betty ; Cavalli, Florence ; Peacock, John ; López, Borja ; Skowron, Patryk ; Zagzag, David ; Lyden, David ; Hoffman, Caitlin ; Cho, Yoon-Jae ; Eberhart, Charles ; MacDonald, Tobey ; Li, Xiao Nan ; Van Meter, Timothy ; Northcott, Paul A. ; Haibe-Kains, Benjamin ; Hawkins, Cynthia ; Rutka, James T. ; Bouffet, Eric ; Pfister, Stefan M. ; Korshunov, Andrey ; Taylor, Michael D. / Medulloblastoma subgroups remain stable across primary and metastatic compartments. In: Acta Neuropathologica. 2015 ; Vol. 129, No. 3. pp. 449-457.
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AU - Luu, Betty

AU - Cavalli, Florence

AU - Peacock, John

AU - López, Borja

AU - Skowron, Patryk

AU - Zagzag, David

AU - Lyden, David

AU - Hoffman, Caitlin

AU - Cho, Yoon-Jae

AU - Eberhart, Charles

AU - MacDonald, Tobey

AU - Li, Xiao Nan

AU - Van Meter, Timothy

AU - Northcott, Paul A.

AU - Haibe-Kains, Benjamin

AU - Hawkins, Cynthia

AU - Rutka, James T.

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AU - Pfister, Stefan M.

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