Literature DB >> 16760442

A biologic definition of Burkitt's lymphoma from transcriptional and genomic profiling.

Michael Hummel1, 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.   

Abstract

BACKGROUND: The 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.
METHODS: We 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.
RESULTS: We 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.
CONCLUSIONS: Our 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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Year:  2006        PMID: 16760442     DOI: 10.1056/NEJMoa055351

Source DB:  PubMed          Journal:  N Engl J Med        ISSN: 0028-4793            Impact factor:   91.245


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