Intertumoral Heterogeneity within Medulloblastoma Subgroups

Florence M.G. Cavalli, Marc Remke, Ladislav Rampasek, John Peacock, David J.H. Shih, Betty Luu, Livia Garzia, Jonathon Torchia, Carolina Nor, A. Sorana Morrissy, Sameer Agnihotri, Yuan Yao Thompson, Claudia M. Kuzan-Fischer, Hamza Farooq, Keren Isaev, Craig Daniels, Byung Kyu Cho, Seung Ki Kim, Kyu Chang Wang, Ji Yeoun LeeWieslawa A. Grajkowska, Marta Perek-Polnik, Alexandre Vasiljevic, Cecile Faure-Conter, Anne Jouvet, Caterina Giannini, Amulya A. Nageswara Rao, Kay Ka Wai Li, Ho Keung Ng, Charles G. Eberhart, Ian F. Pollack, Ronald L. Hamilton, G. Yancey Gillespie, James M. Olson, Sarah Leary, William A. Weiss, Boleslaw Lach, Lola B. Chambless, Reid C. Thompson, Michael K. Cooper, Rajeev Vibhakar, Peter Hauser, Marie Lise C. van Veelen, Johan M. Kros, Pim J. French, Young Shin Ra, Toshihiro Kumabe, Enrique López-Aguilar, Karel Zitterbart, Jaroslav Sterba, Gaetano Finocchiaro, Maura Massimino, Erwin G. Van Meir, Satoru Osuka, Tomoko Shofuda, Almos Klekner, Massimo Zollo, Jeffrey R. Leonard, Joshua B. Rubin, Nada Jabado, Steffen Albrecht, Jaume Mora, Timothy E. Van Meter, Shin Jung, Andrew S. Moore, Andrew R. Hallahan, Jennifer A. Chan, Daniela P.C. Tirapelli, Carlos G. Carlotti, Maryam Fouladi, José Pimentel, Claudia C. Faria, Ali G. Saad, Luca Massimi, Linda M. Liau, Helen Wheeler, Hideo Nakamura, Samer K. Elbabaa, Mario Perezpeña-Diazconti, Fernando Chico Ponce de León, Shenandoah Robinson, Michal Zapotocky, Alvaro Lassaletta, Annie Huang, Cynthia E. Hawkins, Uri Tabori, Eric Bouffet, Ute Bartels, Peter B. Dirks, James T. Rutka, Gary D. Bader, Jüri Reimand, Anna Goldenberg, Vijay Ramaswamy, Michael D. Taylor

Research output: Contribution to journalArticle

268 Scopus citations

Abstract

While molecular subgrouping has revolutionized medulloblastoma classification, the extent of heterogeneity within subgroups is unknown. Similarity network fusion (SNF) applied to genome-wide DNA methylation and gene expression data across 763 primary samples identifies very homogeneous clusters of patients, supporting the presence of medulloblastoma subtypes. After integration of somatic copy-number alterations, and clinical features specific to each cluster, we identify 12 different subtypes of medulloblastoma. Integrative analysis using SNF further delineates group 3 from group 4 medulloblastoma, which is not as readily apparent through analyses of individual data types. Two clear subtypes of infants with Sonic Hedgehog medulloblastoma with disparate outcomes and biology are identified. Medulloblastoma subtypes identified through integrative clustering have important implications for stratification of future clinical trials.

Original languageEnglish (US)
Pages (from-to)737-754.e6
JournalCancer cell
Volume31
Issue number6
DOIs
StatePublished - Jun 12 2017

Keywords

  • copy number
  • gene expression
  • integrative clustering
  • medulloblastoma
  • methylation
  • subgroups

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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    Cavalli, F. M. G., Remke, M., Rampasek, L., Peacock, J., Shih, D. J. H., Luu, B., Garzia, L., Torchia, J., Nor, C., Morrissy, A. S., Agnihotri, S., Thompson, Y. Y., Kuzan-Fischer, C. M., Farooq, H., Isaev, K., Daniels, C., Cho, B. K., Kim, S. K., Wang, K. C., ... Taylor, M. D. (2017). Intertumoral Heterogeneity within Medulloblastoma Subgroups. Cancer cell, 31(6), 737-754.e6. https://doi.org/10.1016/j.ccell.2017.05.005