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

Morin, R.; Johnson, N.; Severson, T.; Mungall, A.; An, J.; Goya, R.; Paul, J.; Boyle, M.; Woolcock, B.; Kuchenbauer, F.; Yap, D.; Humphries, R.; Griffith, O.; Shah, S.; Zhu, H.; Kimbara, M.; Shashkin, P.; Charlot, J.; Tcherpakov, M.; Corbett, R.; Tam, A.; Varhol, Richard; Smailus, D.; Moksa, M.; Zhao, Y.; Delaney, A.; Qian, H.; Birol, I.; Schein, J.; Moore, R.; Holt, R.; Horsman, D.; Connors, J.; Jones, S.; Aparicio, S.; Hirst, M.; Gascoyne, R.; Marra, M.

doi:10.1038/ng.518

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Authors

Morin, R.

Johnson, N.

Severson, T.

Mungall, A.

An, J.

Goya, R.

Paul, J.

Boyle, M.

Woolcock, B.

Kuchenbauer, F.

Yap, D.

Humphries, R.

Griffith, O.

Shah, S.

Zhu, H.

Kimbara, M.

Shashkin, P.

Charlot, J.

Tcherpakov, M.

Corbett, R.

Tam, A.

Varhol, Richard

Smailus, D.

Moksa, M.

Zhao, Y.

Delaney, A.

Qian, H.

Birol, I.

Schein, J.

Moore, R.

Holt, R.

Horsman, D.

Connors, J.

Jones, S.

Aparicio, S.

Hirst, M.

Gascoyne, R.

Marra, M.

Date

2010

Type

Journal Article

Metadata

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Citation

Morin, R. and Johnson, N. and Severson, T. and Mungall, A. and An, J. and Goya, R. and Paul, J. et al. 2010. Somatic mutations altering EZH2 (Tyr641) in follicular and diffuse large B-cell lymphomas of germinal-center origin. Nature Genetics. 42 (2): pp. 181-185.

Source Title

Nature Genetics

DOI

10.1038/ng.518

ISSN

1061-4036

School

Department of Health Policy and Management

URI

http://hdl.handle.net/20.500.11937/42144

Collection

Curtin Research Publications

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-B 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.