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Intertumoral Heterogeneity within Medulloblastoma Subgroups

2017; Cell Press; Volume: 31; Issue: 6 Linguagem: Inglês

10.1016/j.ccell.2017.05.005

1878-3686

Florence M.G. Cavalli, Marc Remke, Ladislav Rampášek, John Peacock, David Shih, Betty Luu, Livia Garzia, Jonathon Torchia, Carolina Nör, A. Sorana Morrissy, Sameer Agnihotri, Yuan Thompson, Claudia M. Kuzan-Fischer, Hamza Farooq, Keren Isaev, Craig Daniels, Byung-Kyu Cho, Seung-Ki Kim, Kyu‐Chang Wang, Ji Yeoun Lee, Wiesława Grajkowska, Marta Perek‐Polnik, Alexandre Vasiljevic, Cécile 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, Bolesław Lach, Lola B. Chambless, Reid C. Thompson, Michael K. Cooper, Rajeev Vibhakar, Péter Hauser, Marie‐Lise C. van Veelen, Johan M. Kros, Pim J. French, Young Seob Shin, Toshihiro Kumabe, Enrique López‐Aguilar, Karel Zitterbart, Jaroslav Štěrba, Gaetano Finocchiaro, Maura Massimino, Erwin G. Van Meir, Satoru Osuka, Tomoko Shofuda, Álmos Klekner, Massimo Zollo, Jeffrey R. Leonard, Joshua B. Rubin, Nada Jabado, Steffen Albrecht, Jaume Mora, Timothy Van Meter, Shin Jung, Andrew S. Moore, Andrew R. Hallahan, Jennifer A. Chan, Daniela Pretti da Cunha Tirapelli, Carlos Gilberto Carlotti, Maryam Fouladi, José Pimentel, Cláudia C. Faria, Ali G. Saad, Luca Massimi, Linda M. Liau, Helen Wheeler, Hideo Nakamura, Samer K. Elbabaa, Mario Pérezpeña-Díazconti, Fernando Chico Ponce de León, Shenandoah Robinson, Michal Zápotocký, Álvaro Lassaletta, Annie Huang, Cynthia Hawkins, Uri Tabori, Éric Bouffet, Ute Bartels, Peter B. Dirks, James T. Rutka, Gary D. Bader, Jüri Reimand, Anna Goldenberg, Vijay Ramaswamy, Michael D. Taylor,

Cancer Genomics and Diagnostics

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.