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The genetic landscape of mutations in Burkitt lymphoma
- Cassandra Love1,
- Zhen Sun1,
- Dereje Jima1,
- Guojie Li1,
- Jenny Zhang1,
- Rodney Miles2,
- Kristy L Richards3,
- Cherie H Dunphy3,
- William W L Choi4,
- Gopesh Srivastava4,
- Patricia L Lugar5,6,
- David A Rizzieri5,6,
- Anand S Lagoo5,6,
- Leon Bernal-Mizrachi7,
- Karen P Mann7,
- Christopher R Flowers7,
- Kikkeri N Naresh8,
- Andrew M Evens9,
- Amy Chadburn10,
- Leo I Gordon10,
- Magdalena B Czader11,
- Javed I Gill12,
- Eric D Hsi13,
- Adrienne Greenough1,
- Andrea B Moffitt1,
- Matthew McKinney1,5,6,
- Anjishnu Banerjee14,
- Vladimir Grubor1,
- Shawn Levy15,
- David B Dunson14 &
- …
- Sandeep S Dave1,5,6
Nature Geneticsvolume 44, pages1321–1325 (2012)Cite this article
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Abstract
Burkitt lymphoma is characterized by deregulation ofMYC, 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, includingID3,GNA13,RET,PIK3R1 and the SWI/SNF genesARID1A andSMARCA4. Our data implicate a number of genes in cancer for the first time, includingCCT6B,SALL3,FTCD andPC.ID3 mutations occurred in 34% of Burkitt lymphomas and not in DLBCLs. We show experimentally thatID3 mutations promote cell cycle progression and proliferation. Our work thus elucidates commonly occurring gene-coding mutations in Burkitt lymphoma and implicatesID3 as a new tumor suppressor gene.
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Acknowledgements
The authors thank S. Sunay and the Georgia Cancer Coalition for support in sample collection. 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. We gratefully acknowledge the generous support of C. Stiefel and D. Stiefel.
Author information
Authors and Affiliations
Duke Institute for Genome Sciences and Policy, Duke University, Durham, North Carolina, USA
Cassandra Love, Zhen Sun, Dereje Jima, Guojie Li, Jenny Zhang, Adrienne Greenough, Andrea B Moffitt, Matthew McKinney, Vladimir Grubor & Sandeep S Dave
Department of Pathology, University of Utah, Salt Lake City, Utah, USA
Rodney Miles
Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, North Carolina, USA
Kristy L Richards & Cherie H Dunphy
Department of Pathology, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China
William W L Choi & Gopesh Srivastava
Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina, USA
Patricia L Lugar, David A Rizzieri, Anand S Lagoo, Matthew McKinney & Sandeep S Dave
Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA
Patricia L Lugar, David A Rizzieri, Anand S Lagoo, Matthew McKinney & Sandeep S Dave
Department of Hematology and Medical Oncology, Emory University, Atlanta, Georgia, USA
Leon Bernal-Mizrachi, Karen P Mann & Christopher R Flowers
Department of Medicine, Imperial College, London, UK
Kikkeri N Naresh
Department of Medicine, University of Massachusetts, Worcester, Massachusetts, USA
Andrew M Evens
Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
Amy Chadburn & Leo I Gordon
Department of Pathology and Laboratory Medicine, Indiana University, Indianapolis, Indiana, USA
Magdalena B Czader
Department of Hematology, Baylor University Medical Center, Dallas, Texas, USA
Javed I Gill
Department of Anatomic Pathology, Cleveland Clinic, Cleveland, Ohio, USA
Eric D Hsi
Department of Statistical Science, Duke University, Durham, North Carolina, USA
Anjishnu Banerjee & David B Dunson
Hudson Alpha Institute for Biotechnology, Huntsville, Alabama, USA
Shawn Levy
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Contributions
C.L., R.M., K.L.R., C.H.D., W.W.L.C., G.S., P.L.L., D.A.R., A.S.L., L.B.-M., K.P.M., C.R.F., K.N.N., A.M.E., A.C., L.I.G., M.B.C., J.I.G., E.D.H., J.Z., G.L., A.G., M.M., S.L. and S.S.D. performed research and edited the manuscript. C.L., J.Z., A.B.M., D.J., Z.S., V.G., A.B., D.B.D. and S.S.D. analyzed data. C.L. and S.S.D. wrote the manuscript.
Corresponding author
Correspondence toSandeep S Dave.
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The authors declare no competing financial interests.
Supplementary information
Supplementary Text and Figures
Supplementary Note and Supplementary Figures 1–10 (PDF 4090 kb)
Supplementary Table 1
Burkitt lymphoma whole genome sequencing variants (XLS 2765 kb)
Supplementary Table 2
Sanger sequence validation (XLS 66 kb)
Supplementary Table 3
Recurrently mutated genes in Burkitt lymphoma (XLS 50 kb)
Supplementary Table 4
Individual variants found in Burkitt lymphoma (XLS 217 kb)
Supplementary Table 5
Patient data (XLS 42 kb)
Supplementary Table 6
Primer sequences (XLS 30 kb)
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Love, C., Sun, Z., Jima, D.et al. The genetic landscape of mutations in Burkitt lymphoma.Nat Genet44, 1321–1325 (2012). https://doi.org/10.1038/ng.2468
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