The genetic landscape of mutations in Burkitt lymphoma

• Type of Material: Article
• Authors: Cassandra Love, Duke University; Zhen Sun, Duke University; Dereje Jima, Duke University; Guojie Li, Duke University; Jenny Zhang, Duke University; Rodney Miles, University of Utah; Kristy L. Richards, University of North Carolina; Cherie H. Dunphy, University of North Carolina; William W. L. Choi, University of Hong Kong; Gopesh Srivastava, University of Hong Kong; Patricia L. Lugar, Duke University; David A. Rizzieri, Duke University; Anand S. Lagoo, Duke University; Leon Bernal-Mizrachi, Emory University; Karen Mann, Emory University; Christopher R Flowers, Emory University; Kikkeri N. Naresh, University of London; Andrew M. Evens, University of Massachusetts; Amy Chadburn, Northwestern University; Leo I. Gordon, Northwestern University; Magdalena B. Czader, Indiana University; Javed I. Gill, Baylor University; Eric D. Hsi, Cleveland Clinic; Adrienne Greenough, Duke University; Andrea B. Moffitt, Duke University; Matthew McKinney, Duke University; Anjishnu Banerjee, Duke University; Vladimir Grubor, Duke University; Shawn Levy, Hudson Alpha Institute for Biotechnology; David B. Dunson, Duke University; Sandeep S. Dave, Duke University
• Language: English
• Date: 2012-12-01
• Publisher: Nature Research (part of Springer Nature)
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2012 Nature America, Inc. All rights reserved.
• Final Published Version (URL): http://dx.doi.org/10.1038/ng.2468
• Title of Journal or Parent Work: Nature Genetics
• ISSN: 1061-4036
• Volume: 44
• Issue: 12
• Start Page: 1321
• End Page: 1325
• Grant/Funding Information: A.B.M. was supported by the Hertz Foundation.; This work was supported through grants R21CA1561686 and R01CA136895 from the National Cancer Institute (S.S.D.).; S.S.D. was also supported by the American Cancer Society.
• Keywords: C-MYC ONCOGENE; SOMATIC MUTATIONS; EXPRESSION; Science & Technology; AMPLIFICATION; Life Sciences & Biomedicine; REVEALS; FREQUENT; GENOME; CANCER; Genetics & Heredity
• Research Categories: Biology, Genetics

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.