• Michael Hummel, Stefan Bentink, Hilmar Berger, Wolfram Klapper, Swen Wessendorf, Thomas F E Barth, Heinz-Wolfram Bernd, Sergio B Cogliatti, Judith Dierlamm, Alfred C Feller, Martin-Leo Hansmann, Eugenia Haralambieva, Lana Harder, Dirk Hasenclever, Michael Kühn, Dido Lenze, Peter Lichter, Jose Ignacio Martin-Subero, Peter Möller, Hans-Konrad Müller-Hermelink, German Ott, Reza M Parwaresch, Christiane Pott, Andreas Rosenwald, Maciej Rosolowski, Carsten Schwaenen, Benjamin Stürzenhofecker, Monika Szczepanowski, Heiko Trautmann, Hans-Heinrich Wacker, Rainer Spang, Markus Loeffler, Lorenz Trümper, Harald Stein, Reiner Siebert, and Molecular Mechanisms in Malignant Lymphomas Network Project of the Deutsche Krebshilfe.
• Institute of Pathology, Campus Benjamin Franklin, Charité Universitätsmedizin, Berlin, Germany.
• N. Engl. J. Med. 2006 Jun 8; 354 (23): 241924302419-30.

BackgroundThe distinction between Burkitt's lymphoma and diffuse large-B-cell lymphoma is unclear. We used transcriptional and genomic profiling to define Burkitt's lymphoma more precisely and to distinguish subgroups in other types of mature aggressive B-cell lymphomas.MethodsWe performed gene-expression profiling using Affymetrix U133A GeneChips with RNA from 220 mature aggressive B-cell lymphomas, including a core group of 8 Burkitt's lymphomas that met all World Health Organization (WHO) criteria. A molecular signature for Burkitt's lymphoma was generated, and chromosomal abnormalities were detected with interphase fluorescence in situ hybridization and array-based comparative genomic hybridization.ResultsWe used the molecular signature for Burkitt's lymphoma to identify 44 cases: 11 had the morphologic features of diffuse large-B-cell lymphomas, 4 were unclassifiable mature aggressive B-cell lymphomas, and 29 had a classic or atypical Burkitt's morphologic appearance. Also, five did not have a detectable IG-myc Burkitt's translocation, whereas the others contained an IG-myc fusion, mostly in simple karyotypes. Of the 176 lymphomas without the molecular signature for Burkitt's lymphoma, 155 were diffuse large-B-cell lymphomas. Of these 155 cases, 21 percent had a chromosomal breakpoint at the myc locus associated with complex chromosomal changes and an unfavorable clinical course.ConclusionsOur molecular definition of Burkitt's lymphoma clarifies and extends the spectrum of the WHO criteria for Burkitt's lymphoma. In mature aggressive B-cell lymphomas without a gene signature for Burkitt's lymphoma, chromosomal breakpoints at the myc locus were associated with an adverse clinical outcome.Copyright 2006 Massachusetts Medical Society.

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