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 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

doi:10.1016/j.ccell.2017.05.005

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Intertumoral Heterogeneity within Medulloblastoma Subgroups

Journal article

Open access

Peer reviewed

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, …

Cancer cell, Vol.31(6), pp.737-754.e6

2017-06-12

DOI: https://doi.org/10.1016/j.ccell.2017.05.005

PMCID: PMC6163053

PMID: 28609654

Abstract

copy number

gene expression

integrative clustering

medulloblastoma

methylation

subgroups

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. [Display omitted] •Medulloblastoma comprises 12 subtypes; 2 WNT, 4 SHH, 3 group 3, and 3 group 4 groups•Heterogeneity within subgroups accounts for previously unexplained variation•Groups 3 and 4 medulloblastoma are molecularly distinct entities•Clinically and biologically relevant subtypes exist for each subgroup Cavalli et al. analyze 763 primary medulloblastoma samples using the similarity network fusion approach. They identify subtypes that have distinct somatic copy-number aberrations, activated pathways, and clinical outcomes within each of the four known subgroups and further delineate group 3 from group 4 MB.

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.113 Brain Imaging; 1.113.977 Medulloblastoma
Web Of Science research areas: Cell Biology; Oncology
ESI research areas: Molecular Biology & Genetics

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Title: Intertumoral Heterogeneity within Medulloblastoma Subgroups
Creators: Florence M.G Cavalli - University of Toronto
Marc Remke - German Cancer Research Center
Ladislav Rampasek - University of Toronto
John Peacock - University of Toronto
David J.H Shih - Hospital for Sick Children
Betty Luu - University of Toronto
Livia Garzia - University of Toronto
Jonathon Torchia - University of Toronto
Carolina Nor - University of Toronto
A. Sorana Morrissy - University of Toronto
Sameer Agnihotri - University of Pittsburgh
Yuan Yao Thompson - University of Toronto
Claudia M Kuzan-Fischer - University of Toronto
Hamza Farooq - University of Toronto
Keren Isaev - Ontario Institute for Cancer Research
Craig Daniels - University of Toronto
Byung-Kyu Cho - Seoul National University
Seung-Ki Kim - Seoul National University
Kyu-Chang Wang - Seoul National University
Ji Yeoun Lee - Seoul National University
Wieslawa A Grajkowska - University of Warsaw
Marta Perek-Polnik - University of Warsaw
Alexandre Vasiljevic - Hospices Civils de Lyon
Cecile Faure-Conter - Institute of Pediatric Hematology and Oncology, Lyon 69008, France
Anne Jouvet - Université de Lyon
Caterina Giannini - Mayo Clinic
Amulya A Nageswara Rao - Division of Pediatric Hematology/Oncology, Mayo Clinic, Rochester, MN 55905, USA
Kay Ka Wai Li - Chinese University of Hong Kong
Ho-Keung Ng - Chinese University of Hong Kong
Charles G Eberhart - Johns Hopkins University
Ian F Pollack - University of Pittsburgh
Ronald L Hamilton - University of Pittsburgh
G. Yancey Gillespie - University of Alabama at Birmingham
James M Olson - University of Washington
Sarah Leary - University of Washington
William A Weiss - University of California, San Francisco
Boleslaw Lach - Hamilton Health Sciences
Lola B Chambless - Vanderbilt University
Reid C Thompson - Vanderbilt University
Michael K Cooper - Vanderbilt University
Rajeev Vibhakar - University of Colorado Denver
Peter Hauser - Semmelweis University
Marie-Lise C van Veelen - Erasmus University Rotterdam
Johan M Kros - Erasmus University Rotterdam
Pim J French - Erasmus University Rotterdam
Young Shin Ra - University of Ulsan
Toshihiro Kumabe - Kitasato University
Enrique López-Aguilar - Mexican Social Security Institute
Karel Zitterbart - Masaryk University
Jaroslav Sterba - Masaryk University
Gaetano Finocchiaro - Department of Neuro-Oncology, Istituto Neurologico Besta, Milan 20133, Italy
Maura Massimino - Fondazione IRCCS Istituto Nazionale Tumori, Milan 20133, Italy
Erwin G Van Meir - Emory University
Satoru Osuka - Emory University
Tomoko Shofuda - Osaka National Hospital
Almos Klekner - University of Debrecen
Massimo Zollo - University of Naples Federico II
Jeffrey R Leonard - Washington University in St. Louis
Joshua B Rubin - Washington University in St. Louis
Nada Jabado - McGill University
Steffen Albrecht - McGill University
Jaume Mora - Developmental Tumor Biology Laboratory, Hospital Sant Joan de Déu, Esplugues de Llobregat, Barcelona 08950, Spain
Timothy E Van Meter - Virginia Commonwealth University
Shin Jung - Chonnam National University
Andrew S Moore - University of Queensland
Andrew R Hallahan - University of Queensland
Jennifer A Chan - University of Calgary
Daniela P.C Tirapelli - University of Sao Paulo
Carlos G Carlotti - Universidade de São Paulo
Maryam Fouladi - University of Cincinnati
José Pimentel - Centro Hospitalar Lisboa Norte
Claudia C Faria - Centro Hospitalar Lisboa Norte
Ali G Saad - University of Arkansas for Medical Sciences
Luca Massimi - Catholic University of America
Linda M Liau - University of California, Los Angeles
Helen Wheeler - University of Sydney
Hideo Nakamura - Kumamoto University
Samer K Elbabaa - Saint Louis University
Mario Perezpeña-Diazconti - Hospital Infantil de México Federico Gómez
Fernando Chico Ponce de León - Hospital Infantil de México Federico Gómez
Shenandoah Robinson - Case Western Reserve University
Michal Zapotocky - University of Toronto
Alvaro Lassaletta - University of Toronto
Annie Huang - University of Toronto
Cynthia E Hawkins - University of Toronto
Uri Tabori - University of Toronto
Eric Bouffet - University of Toronto
Ute Bartels - University of Toronto
Peter B Dirks - University of Toronto
James T Rutka - University of Toronto
Gary D Bader - University of Toronto
Jüri Reimand - Ontario Institute for Cancer Research
Anna Goldenberg - University of Toronto
Vijay Ramaswamy - University of Toronto
Michael D Taylor - University of Toronto
Publication Details: Cancer cell, Vol.31(6), pp.737-754.e6
Publisher: Elsevier Inc
Academic Unit: Miller School of Medicine; UMMG Department of Pathology
Language: English
Resource Type: Journal article
PMID: 28609654
PMCID: PMC6163053
Record Identifier: 991031714133102976