A global assessment of cancer genomic alterations in epigenetic mechanisms

Epigenetics & Chromatin

Matthieu Schapira⁴  Mathieu Lupien¹  Cheryl H Arrowsmith¹  Emily L Denton³  Muhammad A Shah² 

[1] Princess Margaret Cancer Centre and Department of Medical Biophysics, University of Toronto, Toronto M5G 2M9, ON, Canada;Structural Genomics Consortium, University of Toronto, MaRS Centre, South Tower, 101 College Street, Toronto M5G 1L7, ON, Canada;Current address: Courant Institute, New York University, 12th floor, 715 Broadway, New York 10003, USA;Department of Pharmacology and Toxicology, University of Toronto, 1 King’s College Circle, Toronto M5S 1A8, ON, Canada

关键词: RNA-seq;    Amplification;    Mutation;    Chromatin;    Pan-cancer;    Epigenetics;   

Others  :  1115082
DOI  :  10.1186/1756-8935-7-29

 received in 2014-08-12, accepted in 2014-10-14,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Shah et al.; licensee BioMed Central Ltd.

【 图 表 】

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