title: A global assessment of cancer genomic alterations in epigenetic mechanisms.
abstract: BACKGROUND
  The notion that epigenetic mechanisms may be central to cancer initiation and progression is supported by recent next-generation sequencing efforts revealing that genes involved in chromatin-mediated signaling are recurrently mutated in cancer patients.
  
  
  RESULTS
  Here, we analyze mutational and transcriptional profiles from TCGA and the ICGC across a collection 441 chromatin factors and histones. Chromatin factors essential for rapid replication are frequently overexpressed, and those that maintain genome stability frequently mutated. We identify novel mutation hotspots such as K36M in histone H3.1, and uncover a general trend in which transcriptional profiles and somatic mutations in tumor samples favor increased transcriptionally repressive histone methylation, and defective chromatin remodeling.
  
  
  CONCLUSIONS
  This unbiased approach confirms previously published data, uncovers novel cancer-associated aberrations targeting epigenetic mechanisms, and justifies continued monitoring of chromatin-related alterations as a class, as more cancer types and distinct cancer stages are represented in cancer genomics data repositories.
authors.affiliation: Structural Genomics Consortium, University of Toronto, MaRS Centre, South Tower, 101 College Street, Toronto, M5G 1L7 ON Canada.
authors.forename: Muhammad A
authors.initials: MA
authors.lastname: Shah
authors.affiliation: Structural Genomics Consortium, University of Toronto, MaRS Centre, South Tower, 101 College Street, Toronto, M5G 1L7 ON Canada ; Courant Institute, New York University, 12th floor, 715 Broadway, New York, 10003 USA.
authors.forename: Emily L
authors.initials: EL
authors.lastname: Denton
authors.affiliation: Structural Genomics Consortium, University of Toronto, MaRS Centre, South Tower, 101 College Street, Toronto, M5G 1L7 ON Canada ; Princess Margaret Cancer Centre and Department of Medical Biophysics, University of Toronto, Toronto, M5G 2M9 ON Canada.
authors.forename: Cheryl H
authors.initials: CH
authors.lastname: Arrowsmith
authors.affiliation: Princess Margaret Cancer Centre and Department of Medical Biophysics, University of Toronto, Toronto, M5G 2M9 ON Canada.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Lupien
authors.affiliation: Structural Genomics Consortium, University of Toronto, MaRS Centre, South Tower, 101 College Street, Toronto, M5G 1L7 ON Canada ; Department of Pharmacology and Toxicology, University of Toronto, 1 King's College Circle, Toronto, M5S 1A8 ON Canada.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Schapira
keywords: Amplification; Chromatin; Epigenetics; Mutation; Pan-cancer; RNA-seq