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Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma

Ryan D. Morin,María Méndez-Lago,Andrew J. Mungall,Rodrigo Goya,Karen Mungall,Richard Corbett,Nathalie A. Johnson,Tesa Severson,Readman Chiu,Matthew A. Field,Shaun D. Jackman,Martin Krzywinski,David W. Scott,Diane L. Trinh,Jessica Tamura-Wells,Sa Li,Marlo Firme,Sanja Rogić,Malachi Griffith,Susanna Chan,Oleksandr Yakovenko,Irmtraud M. Meyer,Eric Y. Zhao,Duane E. Smailus,Michelle Moksa,Suganthi Chittaranjan,Lisa M. Rimsza,Angela Brooks‐Wilson,John J. Spinelli,Susana Ben-Neriah,Barbara Meissner,Bruce W. Woolcock,Merrill Boyle,Helen McDonald,Angela Tam,Yongjun Zhao,Allen Delaney,Thomas Zeng,Kane Tse,Yaron S.N. Butterfield,İnanç Birol,Robert A. Holt,Jacqueline E. Schein,Douglas E. Horsman,Richard A. Moore,Steven Jones,Joseph M. Connors,Martin Hirst,Randy D. Gascoyne,Marco A. Marra

Biology

Gene

Somatic cell

2011

Follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) are the two most common non-Hodgkin lymphomas (NHLs). Here we sequenced tumour and matched normal DNA from 13 DLBCL cases and one FL case to identify genes with mutations in B-cell NHL. We analysed RNA-seq data from these and another 113 NHLs to identify genes with candidate mutations, and then re-sequenced tumour and matched normal DNA from these cases to confirm 109 genes with multiple somatic mutations. Genes with roles in histone modification were frequent targets of somatic mutation. For example, 32% of DLBCL and 89% of FL cases had somatic mutations in MLL2, which encodes a histone methyltransferase, and 11.4% and 13.4% of DLBCL and FL cases, respectively, had mutations in MEF2B, a calcium-regulated gene that cooperates with CREBBP and EP300 in acetylating histones. Our analysis suggests a previously unappreciated disruption of chromatin biology in lymphomagenesis.

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“Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma” is a paper by Ryan D. Morin María Méndez-Lago Andrew J. Mungall Rodrigo Goya Karen Mungall Richard Corbett Nathalie A. Johnson Tesa Severson Readman Chiu Matthew A. Field Shaun D. Jackman Martin Krzywinski David W. Scott Diane L. Trinh Jessica Tamura-Wells Sa Li Marlo Firme Sanja Rogić Malachi Griffith Susanna Chan Oleksandr Yakovenko Irmtraud M. Meyer Eric Y. Zhao Duane E. Smailus Michelle Moksa Suganthi Chittaranjan Lisa M. Rimsza Angela Brooks‐Wilson John J. Spinelli Susana Ben-Neriah Barbara Meissner Bruce W. Woolcock Merrill Boyle Helen McDonald Angela Tam Yongjun Zhao Allen Delaney Thomas Zeng Kane Tse Yaron S.N. Butterfield İnanç Birol Robert A. Holt Jacqueline E. Schein Douglas E. Horsman Richard A. Moore Steven Jones Joseph M. Connors Martin Hirst Randy D. Gascoyne Marco A. Marra published in 2011. It has an Open Access status of “hybrid”. You can read and download a PDF Full Text of this paper here.