Recurrent mutation of the ID3 gene in Burkitt lymphoma identified by integrated genome, exome and transcriptome sequencing

被引：324

作者：

Richter, Julia ^{[1
]}

Schlesner, Matthias ^{[2
]}

Hoffmann, Steve ^{[3
]}

Kreuz, Markus ^{[4
]}

Leich, Ellen ^{[5
]}

Burkhardt, Birgit ^{[6
,7
]}

Rosolowski, Maciej ^{[4
]}

Ammerpohl, Ole ^{[1
]}

Wagener, Rabea ^{[1
]}

Bernhart, Stephan H. ^{[3
]}

Lenze, Dido ^{[8
]}

Szczepanowski, Monika ^{[9
]}

Paulsen, Maren ^{[10
]}

Lipinski, Simone ^{[10
]}

Russell, Robert B. ^{[11
]}

Adam-Klages, Sabine ^{[12
]}

Apic, Gordana ^{[11
]}

Claviez, Alexander ^{[13
]}

Hasenclever, Dirk ^{[4
]}

Hovestadt, Volker ^{[14
]}

Hornig, Nadine ^{[1
]}

Korbel, Jan O. ^{[15
]}

Kube, Dieter ^{[16
]}

Langenberger, David ^{[3
]}

Lawerenz, Chris ^{[2
]}

Lisfeld, Jasmin ^{[7
]}

Meyer, Katharina ^{[17
]}

Picelli, Simone ^{[14
]}

Pischimarov, Jordan ^{[5
]}

Radlwimmer, Bernhard ^{[14
]}

Rausch, Tobias ^{[15
]}

Rohde, Marius ^{[7
]}

Schilhabel, Markus ^{[10
]}

Scholtysik, Rene ^{[18
]}

Spang, Rainer ^{[17
]}

Trautmann, Heiko ^{[19
]}

Zenz, Thorsten ^{[20
,21
,22
]}

Borkhardt, Arndt ^{[23
]}

Drexler, Hans G. ^{[24
]}

Moeller, Peter ^{[25
]}

MacLeod, Roderick A. F. ^{[24
]}

Pott, Christiane ^{[19
]}

Schreiber, Stefan ^{[26
]}

Truemper, Lorenz ^{[16
]}

Loeffler, Markus ^{[4
]}

Stadler, Peter F. ^{[27
,28
]}

Lichter, Peter ^{[14
]}

Eils, Roland ^{[2
,29
]}

Kueppers, Ralf ^{[18
]}

Hummel, Michael ^{[8
]}

机构：

[1] Univ Kiel, Inst Human Genet, Kiel, Germany

[2] Deutsch Krebsforschungszentrum Heidelberg DKFZ, Div Theoret Bioinformat, Heidelberg, Germany

[3] Univ Leipzig, LIFE Res Ctr Civilizat Dis, Leipzig, Germany

[4] Univ Leipzig, Inst Med Informat Stat & Epidemiol, Leipzig, Germany

[5] Univ Wurzburg, Inst Pathol, Wurzburg, Germany

[6] Univ Hosp Muenster, Munster, Germany

[7] Univ Hosp Giessen, Giessen, Germany

[8] Charite Univ Med Berlin, Inst Pathol, Berlin, Germany

[9] Univ Kiel, Hematopathol Sect, Kiel, Germany

[10] Univ Kiel, Inst Clin Mol Biol, Kiel, Germany

[11] Heidelberg Univ, Cell Networks, Bioquant, Heidelberg, Germany

[12] Univ Kiel, Inst Immunol, Kiel, Germany

[13] Univ Hosp Schleswig Holstein, Dept Pediat, Kiel, Germany

[14] DKFZ, Div Mol Genet, Heidelberg, Germany

[15] EMBL, Genome Biol Res Unit, Heidelberg, Germany

[16] Univ Gottingen, Dept Hematol & Oncol, Gottingen, Germany

[17] Univ Regensburg, Inst Funct Genom, Regensburg, Germany

[18] Univ Duisburg Essen, Sch Med, Inst Cell Biol Canc Res, Essen, Germany

[19] Univ Med Ctr, Dept Internal Med Hematol & Oncol 2, Kiel, Germany

[20] Heidelberg Univ, Dept Med 5, Heidelberg, Germany

[21] Natl Ctr Tumor Dis NCT, Dept Translat Oncol, Heidelberg, Germany

[22] Univ Ulm, Dept Med 3, Ulm, Germany

[23] Univ Dusseldorf, Dept Pediat Oncol Hematol & Clin Immunol, D-40225 Dusseldorf, Germany

[24] German Collect Microorganisms & Cell Cultures, Dept Human & Anim Cell Cultures, Braunschweig, Germany

[25] Univ Ulm, Fac Med, Inst Pathol, Ulm, Germany

[26] Univ Kiel, Dept Gen Internal Med, Kiel, Germany

[27] Univ Leipzig, Dept Comp Sci, Bioinformat Grp, Leipzig, Germany

[28] Univ Leipzig, Interdisciplinary Ctr Bioinformat, Leipzig, Germany

[29] Heidelberg Univ, Inst Pharm & Mol Biotechnol, Bioquant, Heidelberg, Germany

来源：

NATURE GENETICS | 2012年 / 44卷 / 12期

关键词：

B-CELL LYMPHOMA; MYC; INACTIVATION; DIAGNOSIS; PROTEINS;

D O I：

10.1038/ng.2469

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Burkitt lymphoma is a mature aggressive B-cell lymphoma derived from germinal center B cells(1). Its cytogenetic hallmark is the Burkitt translocation t(8;14)(q24;q32) and its variants, which juxtapose the MYC oncogene with one of the three immunoglobulin loci(2). Consequently, MYC is deregulated, resulting in massive perturbation of gene expression(3). Nevertheless, MYC deregulation alone seems not to be sufficient to drive Burkitt lymphomagenesis. By whole-genome, whole-exome and transcriptome sequencing of four prototypical Burkitt lymphomas with immunoglobulin gene (IG)-MYC translocation, we identified seven recurrently mutated genes. One of these genes, ID3, mapped to a region of focal homozygous loss in Burkitt lymphoma(4). In an extended cohort, 36 of 53 molecularly defined Burkitt lymphomas (68%) carried potentially damaging mutations of ID3. These were strongly enriched at somatic hypermutation motifs. Only 6 of 47 other B-cell lymphomas with the IG-MYC translocation (13%) carried ID3 mutations. These findings suggest that cooperation between ID3 inactivation and IG-MYC translocation is a hallmark of Burkitt lymphomagenesis.

引用

页码：1316 / 1320

页数：5

共 28 条

[1] Translocations involving 8q24 in Burkitt lymphoma and other malignant lymphomas: a historical review of cytogenetics in the light of todays knowledge [J].

Boerma, E. G. ;

Siebert, R. ;

Kluin, P. M. ;

Baudis, M. .

LEUKEMIA, 2009, 23 (02) :225-234

[2] Restricting activation-induced cytidine deaminase tumorigenic activity in B lymphocytes [J].

Casellas, Rafael ;

Yamane, Arito ;

Kovalchuk, Alexander L. ;

Potter, Michael .

IMMUNOLOGY, 2009, 126 (03) :316-328

[3] The DEAD-box RNA helicase DDX3 interacts with DDX5, co-localizes with it in the cytoplasm during the G2/M phase of the cycle, and affects its shuttling during mRNP export [J].

Choi, Yeo-Jin ;

Lee, Seong-Gene .

JOURNAL OF CELLULAR BIOCHEMISTRY, 2012, 113 (03) :985-996

[4] Molecular diagnosis of Burkitt's lymphoma [J].

Dave, Sandeep S. ;

Fu, Kai ;

Wright, George W. ;

Lam, Lloyd T. ;

Kluin, Philip ;

Boerma, Evert-Jan ;

Greiner, Timothy C. ;

Weisenburger, Dennis D. ;

Rosenwald, Andreas ;

Ott, German ;

Mueller-Hermelink, Hans-Konrad ;

Gascoyne, Randy D. ;

Delabie, Jan ;

Rimsza, Lisa M. ;

Braziel, Rita M. ;

Grogan, Thomas M. ;

Campo, Elias ;

Jaffe, Elaine S. ;

Dave, Bhavana J. ;

Sanger, Warren ;

Bast, Martin ;

Vose, Julie M. ;

Armitage, James O. ;

Connors, Joseph M. ;

Smeland, Erlend B. ;

Kvaloy, Stein ;

Holte, Harald ;

Fisher, Richard I. ;

Miller, Thomas P. ;

Montserrat, Emilio ;

Wilson, Wyndham H. ;

Bahl, Manisha ;

Zhao, Hong ;

Yang, Liming ;

Powell, John ;

Simon, Richard ;

Chan, Wing C. ;

Staudt, Louis M. .

NEW ENGLAND JOURNAL OF MEDICINE, 2006, 354 (23) :2431-2442

[5] Burkitt Lymphoma: Much More than MYC [J].

Dominguez-Sola, David ;

Dalla-Favera, Riccardo .

CANCER CELL, 2012, 22 (02) :141-142

[6] FBXO11 targets BCL6 for degradation and is inactivated in diffuse large B-cell lymphomas [J].

Duan, Shanshan ;

Cermak, Lukas ;

Pagan, Julia K. ;

Rossi, Mario ;

Martinengo, Cinzia ;

di Celle, Paola Francia ;

Chapuy, Bjoern ;

Shipp, Margaret ;

Chiarle, Roberto ;

Pagano, Michele .

NATURE, 2012, 481 (7379) :90-U100

[7] Fast Mapping of Short Sequences with Mismatches, Insertions and Deletions Using Index Structures [J].

Hoffmann, Steve ;

Otto, Christian ;

Kurtz, Stefan ;

Sharma, Cynthia M. ;

Khaitovich, Philipp ;

Vogel, Joerg ;

Stadler, Peter F. ;

Hackermueller, Joerg .

PLOS COMPUTATIONAL BIOLOGY, 2009, 5 (09)

[8] A biologic definition of Burkitt's lymphoma from transcriptional and genomic profiling [J].

Hummel, Michael ;

Bentink, Stefan ;

Berger, Hilmar ;

Klapper, Wolfram ;

Wessendorf, Swen ;

Barth, Thomas F. E. ;

Bernd, Heinz-Wolfram ;

Cogliatti, Sergio B. ;

Dierlamm, Judith ;

Feller, Alfred C. ;

Hansmann, Martin-Leo ;

Haralambieva, Eugenia ;

Harder, Lana ;

Hasenclever, Dirk ;

Kuehn, Michael ;

Lenze, Dido ;

Lichter, Peter ;

Ignacio Martin-Subero, Jose ;

Moeller, Peter ;

Mueller-Hermelink, Hans-Konrad ;

Ott, German ;

Parwaresch, Reza M. ;

Pott, Christiane ;

Rosenwald, Andreas ;

Rosolowski, Maciej ;

Schwaenen, Carsten ;

Stuerzenhofecker, Benjamin ;

Szczepanowski, Monika ;

Trautmann, Heiko ;

Wacker, Hans-Heinrich ;

Spang, Rainer ;

Loeffler, Markus ;

Truemper, Lorenz ;

Stein, Harald ;

Siebert, Reiner .

NEW ENGLAND JOURNAL OF MEDICINE, 2006, 354 (23) :2419-2430

[9] C-MYC HYPERMUTATION IN BURKITTS-LYMPHOMA [J].

JOHNSTON, JM ;

CARROLL, WL .

LEUKEMIA & LYMPHOMA, 1992, 8 (06) :431-439

[10] E and ID proteins branch out [J].

Kee, Barbara L. .

NATURE REVIEWS IMMUNOLOGY, 2009, 9 (03) :175-184

← 1 2 3 →