The genetic landscape of mutations in Burkitt lymphoma. Nat Genet 2012 Dec;44(12):1321-5
Date
11/13/2012Pubmed ID
23143597Pubmed Central ID
PMC3674561DOI
10.1038/ng.2468Scopus ID
2-s2.0-84870538715 (requires institutional sign-in at Scopus site) 491 CitationsAbstract
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.
Author List
Love C, Sun Z, Jima D, Li G, Zhang J, Miles R, Richards KL, Dunphy CH, Choi WW, Srivastava G, Lugar PL, Rizzieri DA, Lagoo AS, Bernal-Mizrachi L, Mann KP, Flowers CR, Naresh KN, Evens AM, Chadburn A, Gordon LI, Czader MB, Gill JI, Hsi ED, Greenough A, Moffitt AB, McKinney M, Banerjee A, Grubor V, Levy S, Dunson DB, Dave SSAuthor
Anjishnu Banerjee PhD Associate Professor in the Data Science Institute department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Ammonia-LyasesBase Sequence
Burkitt Lymphoma
Cell Line, Tumor
Chaperonin Containing TCP-1
DNA Helicases
DNA-Binding Proteins
GTP-Binding Protein alpha Subunits, G12-G13
Genes, myc
Genome, Human
Glutamate Formimidoyltransferase
Homeodomain Proteins
Humans
Inhibitor of Differentiation Proteins
Intracellular Signaling Peptides and Proteins
Lymphoma, Large B-Cell, Diffuse
Membrane Proteins
Molecular Sequence Data
Multifunctional Enzymes
Mutation
Neoplasm Proteins
Nuclear Proteins
Proto-Oncogene Proteins c-ret
Sequence Analysis, DNA
Transcription Factors
Translocation, Genetic