Biological characterization of adult MYC-translocation-positive mature B-cell lymphomas other than molecular Burkitt lymphoma
Sietse M. Aukema,
Markus Kreuz,
Christian W Kohler,
Maciej Rosolowski,
Dirk Hasenclever,
Michael Hummel,
Ralf Küppers,
Dido Lenze,
German Ott,
Christiane Pott,
Julia Richter,
Andreas Rosenwald,
Monika Szczepanowski,
Carsten Schwaenen,
Harald Stein,
Heiko Trautmann,
Swen Wessendorf,
Lorenz Trümper,
Markus Loeffler,
Rainer Spang,
Philip M. Kluin,
Wolfram Klapper,
Reiner Siebert
Affiliations
Sietse M. Aukema
Institute of Human Genetics, University Hospital Schleswig-Holstein Campus Kiel/Christian-Albrechts University Kiel, Germany;Department of Pathology & Medical Biology, University of Groningen, University Medical Center Groningen, the Netherlands;Department of Hematology, University of Groningen, University Medical Center Groningen, the Netherlands
Markus Kreuz
Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Germany
Christian W Kohler
Statistical Bioinformatics, Institute of Functional Genomics, University of Regensburg, Germany
Maciej Rosolowski
Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Germany
Dirk Hasenclever
Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Germany
Michael Hummel
Institute of Pathology, Campus Benjamin Franklin, Charité–Universitätsmedizin Berlin, Germany
Ralf Küppers
Institute of Cell Biology (Cancer Research), University of Duisburg-Essen, Medical School, Essen, Germany
Dido Lenze
Institute of Pathology, Campus Benjamin Franklin, Charité–Universitätsmedizin Berlin, Germany
German Ott
Department of Clinical Pathology, Robert-Bosch-Krankenhaus, and Dr. Margarete Fischer-Bosch Institute of Clinical Pathology, Stuttgart, Germany
Christiane Pott
Second Medical Department, University Hospital Schleswig-Holstein Campus Kiel/Christian-Albrechts University Kiel, Germany
Julia Richter
Institute of Human Genetics, University Hospital Schleswig-Holstein Campus Kiel/Christian-Albrechts University Kiel, Germany
Andreas Rosenwald
Institute of Pathology, University of Würzburg, Germany
Monika Szczepanowski
Institute of Hematopathology, University Hospital Schleswig-Holstein Campus Kiel/Christian-Albrechts University Kiel, Germany
Carsten Schwaenen
Department of Internal Medicine III, University Hospital of Ulm, Germany
Harald Stein
Institute of Pathology, Campus Benjamin Franklin, Charité–Universitätsmedizin Berlin, Germany
Heiko Trautmann
Second Medical Department, University Hospital Schleswig-Holstein Campus Kiel/Christian-Albrechts University Kiel, Germany
Swen Wessendorf
Department of Internal Medicine III, University Hospital of Ulm, Germany
Lorenz Trümper
Department of Hematology and Oncology, Georg-August University of Göttingen, Germany
Markus Loeffler
Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Germany
Rainer Spang
Statistical Bioinformatics, Institute of Functional Genomics, University of Regensburg, Germany
Philip M. Kluin
Department of Pathology & Medical Biology, University of Groningen, University Medical Center Groningen, the Netherlands
Wolfram Klapper
Department of Clinical Pathology, Robert-Bosch-Krankenhaus, and Dr. Margarete Fischer-Bosch Institute of Clinical Pathology, Stuttgart, Germany
Reiner Siebert
Institute of Human Genetics, University Hospital Schleswig-Holstein Campus Kiel/Christian-Albrechts University Kiel, Germany
Chromosomal translocations affecting the MYC oncogene are the biological hallmark of Burkitt lymphomas but also occur in a subset of other mature B-cell lymphomas. If accompanied by a chromosomal break targeting the BCL2 and/or BCL6 oncogene these MYC translocation-positive (MYC+) lymphomas are called double-hit lymphomas, otherwise the term single-hit lymphomas is applied. In order to characterize the biological features of these MYC+ lymphomas other than Burkitt lymphoma we explored, after exclusion of molecular Burkitt lymphoma as defined by gene expression profiling, the molecular, pathological and clinical aspects of 80 MYC-translocation-positive lymphomas (31 single-hit, 46 double-hit and 3 MYC+-lymphomas with unknown BCL6 status). Comparison of single-hit and double-hit lymphomas revealed no difference in MYC partner (IG/non-IG), genomic complexity, MYC expression or gene expression profile. Double-hit lymphomas more frequently showed a germinal center B-cell-like gene expression profile and had higher IGH and MYC mutation frequencies. Gene expression profiling revealed 130 differentially expressed genes between BCL6+/MYC+ and BCL2+/MYC+ double-hit lymphomas. BCL2+/MYC+ double-hit lymphomas more frequently showed a germinal center B-like gene expression profile. Analysis of all lymphomas according to MYC partner (IG/non-IG) revealed no substantial differences. In this series of lymphomas, in which immunochemotherapy was administered in only a minority of cases, single-hit and double-hit lymphomas had a similar poor outcome in contrast to the outcome of molecular Burkitt lymphoma and lymphomas without the MYC break. Our data suggest that, after excluding molecular Burkitt lymphoma and pediatric cases, MYC+ lymphomas are biologically quite homogeneous with single-hit and double-hit lymphomas as well as IG-MYC and non-IG-MYC+ lymphomas sharing various molecular characteristics.
