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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2010-02

AUTHORS

Ryan D Morin, Nathalie A Johnson, Tesa M Severson, Andrew J Mungall, Jianghong An, Rodrigo Goya, Jessica E Paul, Merrill Boyle, Bruce W Woolcock, Florian Kuchenbauer, Damian Yap, R Keith Humphries, Obi L Griffith, Sohrab Shah, Henry Zhu, Michelle Kimbara, Pavel Shashkin, Jean F Charlot, Marianna Tcherpakov, Richard Corbett, Angela Tam, Richard Varhol, Duane Smailus, Michelle Moksa, Yongjun Zhao, Allen Delaney, Hong Qian, Inanc Birol, Jacqueline Schein, Richard Moore, Robert Holt, Doug E Horsman, Joseph M Connors, Steven Jones, Samuel Aparicio, Martin Hirst, Randy D Gascoyne, Marco A Marra

ABSTRACT

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. More... »

PAGES

181

References to SciGraph publications

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  • Journal

    TITLE

    Nature Genetics

    ISSUE

    2

    VOLUME

    42

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ng.518

    DOI

    http://dx.doi.org/10.1038/ng.518

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1001723375

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/20081860


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