Somatic mutation of EZH2 (Y641) in Follicular and Diffuse Large B-cell Lymphomas of Germinal Center Origin
By Ryan D. Morin, N. Johnson, T. Severson, A. Mungall, Jianghong An, R. Goya, J. E. Paul, M. Boyle, B. Woolcock, F. Kuchenbauer and 28 more. Nature Genetics, 2010
920 citations recorded by the source corpus.
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-κB 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.
Subfields: Molecular Biology
View Paper: https://www.semanticscholar.org/paper/8f6d2641c0f3791a8a14e22eeb2dcba9dcc030c1
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Citations in the corpus
- Polycomb group proteins: multi-faceted regulators of somatic stem cells and cancer. (2010, positive): “Somatic Ezh2 mutations and deletions were found in 22% of germinal center diffuse large B cell lymphomas, 7% follicular lymphomas, and 12%–23% of patients with myelodysplasic and myeloproliferative disorders (Ernst et al., 2010; Morin et al., 2010; Nikoloski et al., 2010).”
- Aberrant epigenetic landscape in cancer: how cellular identity goes awry. (2010, neutral): “*EZH2 (KMT6) H3K27 mutation loss lymphoma Morin et al. (2010) 20081860”
- The Polycomb Complex PRC2 and its Mark in Life (2011, background): “Recurrent somatic mutations that interfere with EZH2 enzymatic activity occur in subtypes of lymphom”
- Lessons from the cancer genome. (2013, neutral): “(An exception is EZH2, in which gain-of-function mutants are observed in follicular lymphoma [Morin et al., 2010], whereas loss-of-function events are seen in myeloid cancers [Jankowska et al.”