Journal article

Integrated (epi)-Genomic Analyses Identify Subgroup-Specific Therapeutic Targets in CNS Rhabdoid Tumors

Jonathon Torchia, Brian Golbourn, Shengrui Feng, King Ching Ho, Patrick Sin-Chan, Alexandre Vasiljevic, Joseph D Norman, Paul Guilhamon, Livia Garzia, Natalia R Agamez, Mei Lu, Tiffany S Chan, Daniel Picard, Pasqualino de Antonellis, Dong-Anh Khuong-Quang, Aline C Planello, Constanze Zeller, Dalia Barsyte-Lovejoy, Lucie Lafay-Cousin, Louis Letourneau Show all

Cancer Cell | CELL PRESS | Published : 2016

Abstract

We recently reported that atypical teratoid rhabdoid tumors (ATRTs) comprise at least two transcriptional subtypes with different clinical outcomes; however, the mechanisms underlying therapeutic heterogeneity remained unclear. In this study, we analyzed 191 primary ATRTs and 10 ATRT cell lines to define the genomic and epigenomic landscape of ATRTs and identify subgroup-specific therapeutic targets. We found ATRTs segregated into three epigenetic subgroups with distinct genomic profiles, SMARCB1 genotypes, and chromatin landscape that correlated with differential cellular responses to a panel of signaling and epigenetic inhibitors. Significantly, we discovered that differential methylation ..

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Grants

Awarded by Genome Canada


Awarded by CCSRI


Funding Acknowledgements

This work was supported by funds from Genome Canada, 110814 (A.H. and N.J.), CCSRI #703279 (A.H. and D.D.C.), b.r.a.i.n.child, Mitchell Duckman, Tal Doron, and Suri Boon foundations (A.H. and J.T.R.) and C17 Childhood Cancer and Blood Disorders Research Network (L.L.C., E.B., A.H). J.T. and P.S.C. are Ontario Graduate Scholars; D.G. and J.D.N. are, respectively, Brain Canada and CIHR Research Fellows. Technical support from V. Lau, A. Ma, and staff of the McGill University and Genome Quebec Innovation Center, the Princess Margaret Genomics Center, the Center for Applied Genomics Toronto, the Rare Brain Tumor Consortium (http://www.rarebraintumorconsortium.ca), tumor banks of contributing centers (Table S8), and tissue contributions from Dr. A. Korshunov are gratefully acknowledged.