A Biologic Definition of Burkitt's Lymphoma from Transcriptional and Genomic Profiling
Michael Hummel, Ph.D., Stefan Bentink, M.S., Hilmar Berger, M.D., Wolfram Klapper, M.D., Swen Wessendorf, M.D., Thomas F.E. Barth, M.D., Heinz-Wolfram Bernd, M.D., Sergio B. Cogliatti, M.D., Judith Dierlamm, M.D., Ph.D., Alfred C. Feller, M.D., Martin-Leo Hansmann, M.D., Eugenia Haralambieva, M.D., Lana Harder, M.D., Dirk Hasenclever, Ph.D., Michael Kühn, Dido Lenze, Ph.D., Peter Lichter, Ph.D., Jose Ignacio Martin-Subero, Ph.D., Peter Möller, M.D., Hans-Konrad Müller-Hermelink, M.D., German Ott, M.D., Reza M. Parwaresch, M.D., Christiane Pott, M.D., Andreas Rosenwald, M.D., Maciej Rosolowski, Ph.D., Carsten Schwaenen, M.D., Benjamin Stürzenhofecker, Ph.D., Monika Szczepanowski, Ph.D., Heiko Trautmann, M.S., Hans-Heinrich Wacker, M.D., Rainer Spang, Ph.D., Markus Loeffler, M.D., Ph.D., Lorenz Trümper, M.D., Harald Stein, M.D., Reiner Siebert, M.D., for the Molecular Mechanisms in Malignant Lymphomas Network Project of the Deutsche Krebshilfe
Background The distinction between Burkitt's lymphoma and diffuselarge-B-cell lymphoma is unclear. We used transcriptional andgenomic profiling to define Burkitt's lymphoma more preciselyand to distinguish subgroups in other types of mature aggressiveB-cell lymphomas.
Methods We performed gene-expression profiling using AffymetrixU133A GeneChips with RNA from 220 mature aggressive B-cell lymphomas,including a core group of 8 Burkitt's lymphomas that met allWorld Health Organization (WHO) criteria. A molecular signaturefor Burkitt's lymphoma was generated, and chromosomal abnormalitieswere detected with interphase fluorescence in situ hybridizationand array-based comparative genomic hybridization.
Results We used the molecular signature for Burkitt's lymphomato identify 44 cases: 11 had the morphologic features of diffuselarge-B-cell lymphomas, 4 were unclassifiable mature aggressiveB-cell lymphomas, and 29 had a classic or atypical Burkitt'smorphologic appearance. Also, five did not have a detectableIG-myc Burkitt's translocation, whereas the others containedan IG-myc fusion, mostly in simple karyotypes. Of the 176 lymphomaswithout the molecular signature for Burkitt's lymphoma, 155were diffuse large-B-cell lymphomas. Of these 155 cases, 21percent had a chromosomal breakpoint at the myc locus associatedwith complex chromosomal changes and an unfavorable clinicalcourse.
Conclusions Our molecular definition of Burkitt's lymphoma clarifiesand extends the spectrum of the WHO criteria for Burkitt's lymphoma.In mature aggressive B-cell lymphomas without a gene signaturefor Burkitt's lymphoma, chromosomal breakpoints at the myc locuswere associated with an adverse clinical outcome.
Source Information
Mr. Bentink and Drs. Berger, Klapper, and Wessendorf contributed equally to this article.
Address reprint requests to Dr. Stein at Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Institute of Pathology, Hindenburgdamm 30, D-12200 Berlin Germany, or at Harald.Stein{at}charite.de.
Genomic Diagnosis of Burkitt's Lymphoma
Lin B. T., Dave S. S., Staudt L. M., Hummel M., Stein H., Siebert R., the Molecular Mechanisms in Malignant Lymphomas Network Project of the Deutsche Krebshilfe
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N Engl J Med 2006;
355:1064-1065, Sep 7, 2006.
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