Somatic mutations altering EZH2 (Tyr641) in follicular and diffuse large B-cell lymphomas of germinal-center origin

Autor:	Hong Qian, Ryan D. Morin, Inanc Birol, Tesa M. Severson, Richard Varhol, Bruce Woolcock, Yongjun Zhao, Richard Corbett, Florian Kuchenbauer, Charlot Jf, Rodrigo Goya, Tcherpakov M, Joseph M. Connors, Marco A. Marra, Douglas E. Horsman, Randy D. Gascoyne, Nathalie A. Johnson, Robert A. Holt, Richard A. Moore, Andrew J. Mungall, Allen Delaney, Samuel Aparicio, Angela K Y Tam, Hao Zhu, Michelle Moksa, Jacquie Schein, Shashkin P, Martin Hirst, Damian Yap, Jianghong An, Steven J.M. Jones, Kimbara M, Humphries Rk, Paul Je, Merrill Boyle, Obi L. Griffith, Sohrab P. Shah, Duane E Smailus
Rok vydání:	2010
Předmět:	Male Somatic cell DNA Mutational Analysis 0302 clinical medicine Lymphoma Follicular 0303 health sciences EZH2 Polycomb Repressive Complex 2 Exons Middle Aged PRC2 DNA-Binding Proteins Gene Expression Regulation Neoplastic medicine.anatomical_structure 030220 oncology & carcinogenesis Histone methyltransferase Female lipids (amino acids peptides and proteins) Lymphoma Large B-Cell Diffuse epigenetic Adult Molecular Sequence Data macromolecular substances Biology Article 03 medical and health sciences Germline mutation Genetics medicine Humans Enhancer of Zeste Homolog 2 Protein Amino Acid Sequence genome B cell Aged 030304 developmental biology Base Sequence Genome Human Gene Expression Profiling fungi Germinal center Germinal Center medicine.disease Molecular biology Lymphoma Mutation Tyrosine Mutant Proteins RNA-seq WTSS transcriptome Diffuse large B-cell lymphoma Transcription Factors
Zdroj:	Nature genetics
ISSN:	1546-1718 1061-4036
DOI:	10.1038/ng.518
Popis:	Follicular lymphoma (FL) and the GCB subtype of diffuse large B-cell lymphoma (DLBCL) derive from germinal center B cells. Targeted resequencing studies have revealed mutations in various genes encoding proteins in the NF-kappaB pathway that contribute to the activated B-cell (ABC) DLBCL subtype, but thus far few GCB-specific mutations have been identified. Here we report recurrent somatic mutations affecting the polycomb-group oncogene EZH2, which encodes a histone methyltransferase responsible for trimethylating Lys27 of histone H3 (H3K27). After the recent discovery of mutations in KDM6A (UTX), which encodes the histone H3K27me3 demethylase UTX, in several cancer types, EZH2 is the second histone methyltransferase gene found to be mutated in cancer. These mutations, which result in the replacement of a single tyrosine in the SET domain of the EZH2 protein (Tyr641), occur in 21.7% of GCB DLBCLs and 7.2% of FLs and are absent from ABC DLBCLs. Our data are consistent with the notion that EZH2 proteins with mutant Tyr641 have reduced enzymatic activity in vitro.
Databáze:	OpenAIRE
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