title: Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma.
abstract: 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.
authors.affiliation: Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z 1L3, Canada.
authors.forename: Ryan D
authors.initials: RD
authors.lastname: Morin
authors.forename: Maria
authors.initials: M
authors.lastname: Mendez-Lago
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Mungall
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Goya
authors.forename: Karen L
authors.initials: KL
authors.lastname: Mungall
authors.forename: Richard D
authors.initials: RD
authors.lastname: Corbett
authors.forename: Nathalie A
authors.initials: NA
authors.lastname: Johnson
authors.forename: Tesa M
authors.initials: TM
authors.lastname: Severson
authors.forename: Readman
authors.initials: R
authors.lastname: Chiu
authors.forename: Matthew
authors.initials: M
authors.lastname: Field
authors.forename: Shaun
authors.initials: S
authors.lastname: Jackman
authors.forename: Martin
authors.initials: M
authors.lastname: Krzywinski
authors.forename: David W
authors.initials: DW
authors.lastname: Scott
authors.forename: Diane L
authors.initials: DL
authors.lastname: Trinh
authors.forename: Jessica
authors.initials: J
authors.lastname: Tamura-Wells
authors.forename: Sa
authors.initials: S
authors.lastname: Li
authors.forename: Marlo R
authors.initials: MR
authors.lastname: Firme
authors.forename: Sanja
authors.initials: S
authors.lastname: Rogic
authors.forename: Malachi
authors.initials: M
authors.lastname: Griffith
authors.forename: Susanna
authors.initials: S
authors.lastname: Chan
authors.forename: Oleksandr
authors.initials: O
authors.lastname: Yakovenko
authors.forename: Irmtraud M
authors.initials: IM
authors.lastname: Meyer
authors.forename: Eric Y
authors.initials: EY
authors.lastname: Zhao
authors.forename: Duane
authors.initials: D
authors.lastname: Smailus
authors.forename: Michelle
authors.initials: M
authors.lastname: Moksa
authors.forename: Suganthi
authors.initials: S
authors.lastname: Chittaranjan
authors.forename: Lisa
authors.initials: L
authors.lastname: Rimsza
authors.forename: Angela
authors.initials: A
authors.lastname: Brooks-Wilson
authors.forename: John J
authors.initials: JJ
authors.lastname: Spinelli
authors.forename: Susana
authors.initials: S
authors.lastname: Ben-Neriah
authors.forename: Barbara
authors.initials: B
authors.lastname: Meissner
authors.forename: Bruce
authors.initials: B
authors.lastname: Woolcock
authors.forename: Merrill
authors.initials: M
authors.lastname: Boyle
authors.forename: Helen
authors.initials: H
authors.lastname: McDonald
authors.forename: Angela
authors.initials: A
authors.lastname: Tam
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Zhao
authors.forename: Allen
authors.initials: A
authors.lastname: Delaney
authors.forename: Thomas
authors.initials: T
authors.lastname: Zeng
authors.forename: Kane
authors.initials: K
authors.lastname: Tse
authors.forename: Yaron
authors.initials: Y
authors.lastname: Butterfield
authors.forename: Inanç
authors.initials: I
authors.lastname: Birol
authors.forename: Rob
authors.initials: R
authors.lastname: Holt
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Schein
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Horsman
authors.forename: Richard
authors.initials: R
authors.lastname: Moore
authors.forename: Steven J M
authors.initials: SJ
authors.lastname: Jones
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Connors
authors.forename: Martin
authors.initials: M
authors.lastname: Hirst
authors.forename: Randy D
authors.initials: RD
authors.lastname: Gascoyne
authors.forename: Marco A
authors.initials: MA
authors.lastname: Marra
mesh_terms: D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015894:Genome, Human / Q000235:genetics; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics; D008224:Lymphoma, Follicular / Q000201:enzymology / Q000235:genetics; D016403:Lymphoma, Large B-Cell, Diffuse / Q000201:enzymology / Q000235:genetics; D008228:Lymphoma, Non-Hodgkin / Q000201:enzymology / Q000235:genetics*; D026161:MADS Domain Proteins / Q000235:genetics / Q000378:metabolism; D064326:MEF2 Transcription Factors; D009154:Mutation / Q000235:genetics*; D018006:Myogenic Regulatory Factors / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D002843:Chromatin; D004268:DNA-Binding Proteins; D006657:Histones; C120898:KMT2D protein, human; D026161:MADS Domain Proteins; D064326:MEF2 Transcription Factors; C578038:MEF2B protein, human; D018006:Myogenic Regulatory Factors; D009363:Neoplasm Proteins; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D051548:Histone Acetyltransferases