title: The genetic landscape of mutations in Burkitt lymphoma.
abstract: Burkitt lymphoma is characterized by deregulation of MYC, but the contribution of other genetic mutations to the disease is largely unknown. Here, we describe the first completely sequenced genome from a Burkitt lymphoma tumor and germline DNA from the same affected individual. We further sequenced the exomes of 59 Burkitt lymphoma tumors and compared them to sequenced exomes from 94 diffuse large B-cell lymphoma (DLBCL) tumors. We identified 70 genes that were recurrently mutated in Burkitt lymphomas, including ID3, GNA13, RET, PIK3R1 and the SWI/SNF genes ARID1A and SMARCA4. Our data implicate a number of genes in cancer for the first time, including CCT6B, SALL3, FTCD and PC. ID3 mutations occurred in 34% of Burkitt lymphomas and not in DLBCLs. We show experimentally that ID3 mutations promote cell cycle progression and proliferation. Our work thus elucidates commonly occurring gene-coding mutations in Burkitt lymphoma and implicates ID3 as a new tumor suppressor gene.
authors.affiliation: Duke Institute for Genome Sciences and Policy, Duke University, Durham, NC, USA.
authors.forename: Cassandra
authors.initials: C
authors.lastname: Love
authors.forename: Zhen
authors.initials: Z
authors.lastname: Sun
authors.forename: Dereje
authors.initials: D
authors.lastname: Jima
authors.forename: Guojie
authors.initials: G
authors.lastname: Li
authors.forename: Jenny
authors.initials: J
authors.lastname: Zhang
authors.forename: Rodney
authors.initials: R
authors.lastname: Miles
authors.forename: Kristy L
authors.initials: KL
authors.lastname: Richards
authors.forename: Cherie H
authors.initials: CH
authors.lastname: Dunphy
authors.forename: William W L
authors.initials: WW
authors.lastname: Choi
authors.forename: Gopesh
authors.initials: G
authors.lastname: Srivastava
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Lugar
authors.forename: David A
authors.initials: DA
authors.lastname: Rizzieri
authors.forename: Anand S
authors.initials: AS
authors.lastname: Lagoo
authors.forename: Leon
authors.initials: L
authors.lastname: Bernal-Mizrachi
authors.forename: Karen P
authors.initials: KP
authors.lastname: Mann
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Flowers
authors.forename: Kikkeri N
authors.initials: KN
authors.lastname: Naresh
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Evens
authors.forename: Amy
authors.initials: A
authors.lastname: Chadburn
authors.forename: Leo I
authors.initials: LI
authors.lastname: Gordon
authors.forename: Magdalena B
authors.initials: MB
authors.lastname: Czader
authors.forename: Javed I
authors.initials: JI
authors.lastname: Gill
authors.forename: Eric D
authors.initials: ED
authors.lastname: Hsi
authors.forename: Adrienne
authors.initials: A
authors.lastname: Greenough
authors.forename: Andrea B
authors.initials: AB
authors.lastname: Moffitt
authors.forename: Matthew
authors.initials: M
authors.lastname: McKinney
authors.forename: Anjishnu
authors.initials: A
authors.lastname: Banerjee
authors.forename: Vladimir
authors.initials: V
authors.lastname: Grubor
authors.forename: Shawn
authors.initials: S
authors.lastname: Levy
authors.forename: David B
authors.initials: DB
authors.lastname: Dunson
authors.forename: Sandeep S
authors.initials: SS
authors.lastname: Dave
mesh_terms: D000642:Ammonia-Lyases / Q000235:genetics; D001483:Base Sequence; D002051:Burkitt Lymphoma / Q000235:genetics*; D045744:Cell Line, Tumor; D056404:Chaperonin Containing TCP-1 / Q000235:genetics; D004265:DNA Helicases / Q000235:genetics; D004268:DNA-Binding Proteins; D044365:GTP-Binding Protein alpha Subunits, G12-G13 / Q000235:genetics; D016259:Genes, myc / Q000235:genetics; D015894:Genome, Human; D051042:Glutamate Formimidoyltransferase / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D051796:Inhibitor of Differentiation Proteins / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D008969:Molecular Sequence Data; D064251:Multifunctional Enzymes; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics; D014178:Translocation, Genetic
chemical_list: C112476:ARID1A protein, human; C533303:CCT6B protein, human; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D051796:Inhibitor of Differentiation Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D064251:Multifunctional Enzymes; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C521076:PIK3IP1 protein, human; C484466:SALL3 protein, human; D014157:Transcription Factors; C075640:ID3 protein, human; C494848:FTCD protein, human; D051042:Glutamate Formimidoyltransferase; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human; D056404:Chaperonin Containing TCP-1; C084108:SMARCA4 protein, human; D004265:DNA Helicases; D044365:GTP-Binding Protein alpha Subunits, G12-G13; D000642:Ammonia-Lyases