Burkitt lymphoma is a mature aggressive B-cell lymphoma derived from germinal center B cells. 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. Consequently, MYC is deregulated, resulting in massive perturbation of gene expression. 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. 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.
%0 Journal Article
%1 Richter2012
%A Richter, Julia
%A Schlesner, Matthias
%A Hoffmann, Steve
%A Kreuz, Markus
%A Leich, Ellen
%A Burkhardt, Birgit
%A Rosolowski, Maciej
%A Ammerpohl, Ole
%A Wagener, Rabea
%A Bernhart, Stephan H.
%A Lenze, Dido
%A Szczepanowski, Monika
%A Paulsen, Maren
%A Lipinski, Simone
%A Russell, Robert B.
%A Adam-Klages, Sabine
%A Apic, Gordana
%A Claviez, Alexander
%A Hasenclever, Dirk
%A Hovestadt, Volker
%A Hornig, Nadine
%A Korbel, Jan O.
%A Kube, Dieter
%A Langenberger, David
%A Lawerenz, Chris
%A Lisfeld, Jasmin
%A Meyer, Katharina
%A Picelli, Simone
%A Pischimarov, Jordan
%A Radlwimmer, Bernhard
%A Rausch, Tobias
%A Rohde, Marius
%A Schilhabel, Markus
%A Scholtysik, René
%A Spang, Rainer
%A Trautmann, Heiko
%A Zenz, Thorsten
%A Borkhardt, Arndt
%A Drexler, Hans G.
%A Möller, Peter
%A MacLeod, Roderick A F.
%A Pott, Christiane
%A Schreiber, Stefan
%A Trümper, Lorenz
%A Loeffler, Markus
%A Stadler, Peter F.
%A Lichter, Peter
%A Eils, Roland
%A Küppers, Ralf
%A Hummel, Michael
%A Klapper, Wolfram
%A Rosenstiel, Philip
%A Rosenwald, Andreas
%A Brors, Benedikt
%A Siebert, Reiner
%A ICGC MMML-Seq Project,
%D 2012
%J Nat Genet
%K 14, 8, Analysis, Base Burkitt Chromosome Chromosomes, Cohort DNA; Data; Differentiation Female; Genes, Genetic, Genome, Human, Human; Humans; Hypermutation, Immunoglobulin; Inhibitor Lymphoma, Male; Mapping; Molecular Mutation; Neoplasm Pair Proteins, Sequence Sequence; Somatic Studies; Transcriptome, Translocation, genetics genetics; myc, of
%N 12
%P 1316--1320
%R 10.1038/ng.2469
%T Recurrent mutation of the ID3 gene in Burkitt lymphoma identified by integrated genome, exome and transcriptome sequencing.
%U http://dx.doi.org/10.1038/ng.2469
%V 44
%X Burkitt lymphoma is a mature aggressive B-cell lymphoma derived from germinal center B cells. 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. Consequently, MYC is deregulated, resulting in massive perturbation of gene expression. 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. 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.
@article{Richter2012,
__markedentry = {[bbrors:6]},
abstract = {Burkitt lymphoma is a mature aggressive B-cell lymphoma derived from germinal center B cells. 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. Consequently, MYC is deregulated, resulting in massive perturbation of gene expression. 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. 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.},
added-at = {2015-04-09T12:36:21.000+0200},
author = {Richter, Julia and Schlesner, Matthias and Hoffmann, Steve and Kreuz, Markus and Leich, Ellen and Burkhardt, Birgit and Rosolowski, Maciej and Ammerpohl, Ole and Wagener, Rabea and Bernhart, Stephan H. and Lenze, Dido and Szczepanowski, Monika and Paulsen, Maren and Lipinski, Simone and Russell, Robert B. and Adam-Klages, Sabine and Apic, Gordana and Claviez, Alexander and Hasenclever, Dirk and Hovestadt, Volker and Hornig, Nadine and Korbel, Jan O. and Kube, Dieter and Langenberger, David and Lawerenz, Chris and Lisfeld, Jasmin and Meyer, Katharina and Picelli, Simone and Pischimarov, Jordan and Radlwimmer, Bernhard and Rausch, Tobias and Rohde, Marius and Schilhabel, Markus and Scholtysik, Ren{\'{e}} and Spang, Rainer and Trautmann, Heiko and Zenz, Thorsten and Borkhardt, Arndt and Drexler, Hans G. and M{\"{o}}ller, Peter and MacLeod, Roderick A F. and Pott, Christiane and Schreiber, Stefan and Tr{\"{u}}mper, Lorenz and Loeffler, Markus and Stadler, Peter F. and Lichter, Peter and Eils, Roland and K{\"{u}}ppers, Ralf and Hummel, Michael and Klapper, Wolfram and Rosenstiel, Philip and Rosenwald, Andreas and Brors, Benedikt and Siebert, Reiner and {ICGC MMML-Seq Project}},
biburl = {https://www.bibsonomy.org/bibtex/2e750c90b8e1e825201a025249af87b4a/bbrors},
doi = {10.1038/ng.2469},
institution = {Institute of Human Genetics, Christian-Albrechts-University, Kiel, Germany.},
interhash = {989e9c628b14bbda272017e8d7b4fee1},
intrahash = {e750c90b8e1e825201a025249af87b4a},
journal = {Nat Genet},
keywords = {14, 8, Analysis, Base Burkitt Chromosome Chromosomes, Cohort DNA; Data; Differentiation Female; Genes, Genetic, Genome, Human, Human; Humans; Hypermutation, Immunoglobulin; Inhibitor Lymphoma, Male; Mapping; Molecular Mutation; Neoplasm Pair Proteins, Sequence Sequence; Somatic Studies; Transcriptome, Translocation, genetics genetics; myc, of},
language = {eng},
medline-pst = {ppublish},
month = Dec,
number = 12,
owner = {bbrors},
pages = {1316--1320},
pii = {ng.2469},
pmid = {23143595},
timestamp = {2015-04-09T12:36:21.000+0200},
title = {Recurrent mutation of the ID3 gene in Burkitt lymphoma identified by integrated genome, exome and transcriptome sequencing.},
url = {http://dx.doi.org/10.1038/ng.2469},
volume = 44,
year = 2012
}