Intertumoral Heterogeneity within Medulloblastoma Subgroups.

Authors:
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 Lee Wieslawa 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

Cancer Cell 2017 06;31(6):737-754.e6

The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A1, Canada; Division of Neurosurgery, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada. Electronic address:

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.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ccell.2017.05.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6163053PMC
June 2017
81 Reads

Publication Analysis

Top Keywords

medulloblastoma subtypes
8
medulloblastoma
7
identify subtypes
4
cluster identify
4
specific cluster
4
features specific
4
subtypes medulloblastoma
4
integrative analysis
4
delineates group
4
group group
4
snf delineates
4
analysis snf
4
clinical features
4
medulloblastoma integrative
4
copy-number alterations
4
patients supporting
4
clusters patients
4
homogeneous clusters
4
identifies homogeneous
4
supporting presence
4

Similar Publications