Molecular profiling of pediatric mature B-cell lymphoma treated in population-based prospective clinical trials

The spectrum of entities, the therapeutic strategy, and the outcome of mature aggressive B-cell non-Hodgkin lymphomas (maB-NHLs) differs between children and adolescents on the one hand and adult patients on the other. Whereas adult maB-NHLs have been studied in detail, data on molecular profiling o...

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Published in	Blood Vol. 112; no. 4; pp. 1374 - 1381
Main Authors	Klapper, Wolfram, Szczepanowski, Monika, Burkhardt, Birgit, Berger, Hilmar, Rosolowski, Maciej, Bentink, Stefan, Schwaenen, Carsten, Wessendorf, Swen, Spang, Rainer, Möller, Peter, Hansmann, Martin Leo, Bernd, Heinz-Wolfram, Ott, German, Hummel, Michael, Stein, Harald, Loeffler, Markus, Trümper, Lorenz, Zimmermann, Martin, Reiter, Alfred, Siebert, Reiner
Format	Journal Article
Language	English
Published	Washington, DC Elsevier Inc 15.08.2008 The Americain Society of Hematology
Subjects	Adolescent Adult Age Factors Antineoplastic Combined Chemotherapy Protocols - therapeutic use Biological and medical sciences Burkitt Lymphoma - diagnosis Burkitt Lymphoma - genetics Clinical Trials as Topic Female Gene Expression Profiling Hematologic and hematopoietic diseases Humans Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Lymphoma, B-Cell - diagnosis Lymphoma, B-Cell - drug therapy Lymphoma, B-Cell - genetics Lymphoma, Large B-Cell, Diffuse - diagnosis Lymphoma, Large B-Cell, Diffuse - genetics Male Medical sciences Middle Aged Treatment Outcome Human Prospective Pediatrics Treatment Hematology Lymphoproliferative syndrome Clinical trial Malignant hemopathy B-Lymphocyte Child Lymphoma Cancer
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ISSN	0006-4971 1528-0020 1528-0020
DOI	10.1182/blood-2008-01-136465

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Abstract	The spectrum of entities, the therapeutic strategy, and the outcome of mature aggressive B-cell non-Hodgkin lymphomas (maB-NHLs) differs between children and adolescents on the one hand and adult patients on the other. Whereas adult maB-NHLs have been studied in detail, data on molecular profiling of pediatric maB-NHLs are hitherto lacking. We analyzed 65 cases of maB-NHL from patients up to 18 years of age by gene expression profiling, matrix comparative genomic hybridization (CGH), fluorescent in situ hybridization (FISH), and immunohistochemistry. The majority of the analyzed pediatric patients were treated within prospective trials (n = 49). We compared this group to a series of 182 previously published cases of adult maB-NHL. Gene expression profiling reclassified 31% of morphologically defined diffuse large B-cell lymphomas as molecular Burkitt lymphoma (mBL). The subgroups obtained by molecular reclassification did not show any difference in outcome in children treated with the NHL-Berlin-Frankfurt-Muenster (BFM) protocols. No differences were detectable between pediatric and adult mBL with regard to gene expression or chromosomal imbalances. This is the first report on molecular profiling of pediatric B-NHL showing mBL to be much more prominent in children than suggested by morphologic assessment. Based on molecular profiling mBL is a molecularly homogeneous disease across children and adults.
AbstractList	The spectrum of entities, the therapeutic strategy, and the outcome of mature aggressive B-cell non-Hodgkin lymphomas (maB-NHLs) differs between children and adolescents on the one hand and adult patients on the other. Whereas adult maB-NHLs have been studied in detail, data on molecular profiling of pediatric maB-NHLs are hitherto lacking. We analyzed 65 cases of maB-NHL from patients up to 18 years of age by gene expression profiling, matrix comparative genomic hybridization (CGH), fluorescent in situ hybridization (FISH), and immunohistochemistry. The majority of the analyzed pediatric patients were treated within prospective trials (n = 49). We compared this group to a series of 182 previously published cases of adult maB-NHL. Gene expression profiling reclassified 31% of morphologically defined diffuse large B-cell lymphomas as molecular Burkitt lymphoma (mBL). The subgroups obtained by molecular reclassification did not show any difference in outcome in children treated with the NHL-Berlin-Frankfurt-Muenster (BFM) protocols. No differences were detectable between pediatric and adult mBL with regard to gene expression or chromosomal imbalances. This is the first report on molecular profiling of pediatric B-NHL showing mBL to be much more prominent in children than suggested by morphologic assessment. Based on molecular profiling mBL is a molecularly homogeneous disease across children and adults. The spectrum of entities, the therapeutic strategy, and the outcome of mature aggressive B-cell non-Hodgkin lymphomas (maB-NHLs) differs between children and adolescents on the one hand and adult patients on the other. Whereas adult maB-NHLs have been studied in detail, data on molecular profiling of pediatric maB-NHLs are hitherto lacking. We analyzed 65 cases of maB-NHL from patients up to 18 years of age by gene expression profiling, matrix comparative genomic hybridization (CGH), fluorescent in situ hybridization (FISH), and immunohistochemistry. The majority of the analyzed pediatric patients were treated within prospective trials (n = 49). We compared this group to a series of 182 previously published cases of adult maB-NHL. Gene expression profiling reclassified 31% of morphologically defined diffuse large B-cell lymphomas as molecular Burkitt lymphoma (mBL). The subgroups obtained by molecular reclassification did not show any difference in outcome in children treated with the NHL-Berlin-Frankfurt-Muenster (BFM) protocols. No differences were detectable between pediatric and adult mBL with regard to gene expression or chromosomal imbalances. This is the first report on molecular profiling of pediatric B-NHL showing mBL to be much more prominent in children than suggested by morphologic assessment. Based on molecular profiling mBL is a molecularly homogeneous disease across children and adults.The spectrum of entities, the therapeutic strategy, and the outcome of mature aggressive B-cell non-Hodgkin lymphomas (maB-NHLs) differs between children and adolescents on the one hand and adult patients on the other. Whereas adult maB-NHLs have been studied in detail, data on molecular profiling of pediatric maB-NHLs are hitherto lacking. We analyzed 65 cases of maB-NHL from patients up to 18 years of age by gene expression profiling, matrix comparative genomic hybridization (CGH), fluorescent in situ hybridization (FISH), and immunohistochemistry. The majority of the analyzed pediatric patients were treated within prospective trials (n = 49). We compared this group to a series of 182 previously published cases of adult maB-NHL. Gene expression profiling reclassified 31% of morphologically defined diffuse large B-cell lymphomas as molecular Burkitt lymphoma (mBL). The subgroups obtained by molecular reclassification did not show any difference in outcome in children treated with the NHL-Berlin-Frankfurt-Muenster (BFM) protocols. No differences were detectable between pediatric and adult mBL with regard to gene expression or chromosomal imbalances. This is the first report on molecular profiling of pediatric B-NHL showing mBL to be much more prominent in children than suggested by morphologic assessment. Based on molecular profiling mBL is a molecularly homogeneous disease across children and adults.
Author	Szczepanowski, Monika Reiter, Alfred Stein, Harald Bentink, Stefan Siebert, Reiner Hansmann, Martin Leo Klapper, Wolfram Berger, Hilmar Bernd, Heinz-Wolfram Ott, German Wessendorf, Swen Rosolowski, Maciej Hummel, Michael Spang, Rainer Burkhardt, Birgit Schwaenen, Carsten Trümper, Lorenz Zimmermann, Martin Möller, Peter Loeffler, Markus
Author_xml	– sequence: 1 givenname: Wolfram surname: Klapper fullname: Klapper, Wolfram email: wklapper@path.uni-kiel.de organization: Department of Pathology, Hematopathology Section and Lymph Node Registry, University Hospital Schleswig-Holstein, Campus Kiel/Christian-Albrechts-University Kiel, Germany – sequence: 2 givenname: Monika surname: Szczepanowski fullname: Szczepanowski, Monika organization: Department of Pathology, Hematopathology Section and Lymph Node Registry, University Hospital Schleswig-Holstein, Campus Kiel/Christian-Albrechts-University Kiel, Germany – sequence: 3 givenname: Birgit surname: Burkhardt fullname: Burkhardt, Birgit organization: NHL-BFM Study Center, Department of Pediatric Hematology and Oncology, Justus-Liebig-University, Giessen – sequence: 4 givenname: Hilmar surname: Berger fullname: Berger, Hilmar organization: Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Germany – sequence: 5 givenname: Maciej surname: Rosolowski fullname: Rosolowski, Maciej organization: Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Germany – sequence: 6 givenname: Stefan surname: Bentink fullname: Bentink, Stefan organization: Institute of Functional Genomics, University of Regensburg, Germany – sequence: 7 givenname: Carsten surname: Schwaenen fullname: Schwaenen, Carsten organization: Cytogenetic and Molecular Diagnostics, Internal Medicine III, University Hospital of Ulm, Germany – sequence: 8 givenname: Swen surname: Wessendorf fullname: Wessendorf, Swen organization: Cytogenetic and Molecular Diagnostics, Internal Medicine III, University Hospital of Ulm, Germany – sequence: 9 givenname: Rainer surname: Spang fullname: Spang, Rainer organization: Institute of Functional Genomics, University of Regensburg, Germany – sequence: 10 givenname: Peter surname: Möller fullname: Möller, Peter organization: Institute of Pathology, University Hospital of Ulm, Germany – sequence: 11 givenname: Martin Leo surname: Hansmann fullname: Hansmann, Martin Leo organization: Institute of Pathology, University Hospital of Frankfurt, Germany – sequence: 12 givenname: Heinz-Wolfram surname: Bernd fullname: Bernd, Heinz-Wolfram organization: Department of Pathology, University Hospital Schleswig-Holstein, Campus Lübeck, Germany – sequence: 13 givenname: German surname: Ott fullname: Ott, German organization: Institute of Pathology, University of Würzburg, Stuttgart, Germany – sequence: 14 givenname: Michael surname: Hummel fullname: Hummel, Michael organization: Institute of Pathology, Campus Benjamin Franklin, Charité–Universitätsmedizin Berlin, Germany – sequence: 15 givenname: Harald surname: Stein fullname: Stein, Harald organization: Institute of Pathology, Campus Benjamin Franklin, Charité–Universitätsmedizin Berlin, Germany – sequence: 16 givenname: Markus surname: Loeffler fullname: Loeffler, Markus organization: Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Germany – sequence: 17 givenname: Lorenz surname: Trümper fullname: Trümper, Lorenz organization: Department of Hematology and Oncology, Georg-August University of Göttingen, Germany – sequence: 18 givenname: Martin surname: Zimmermann fullname: Zimmermann, Martin organization: NHL-BFM Study Center, Department of Pediatric Hematology and Oncology, Justus-Liebig-University, Giessen – sequence: 19 givenname: Alfred surname: Reiter fullname: Reiter, Alfred organization: NHL-BFM Study Center, Department of Pediatric Hematology and Oncology, Justus-Liebig-University, Giessen – sequence: 20 givenname: Reiner surname: Siebert fullname: Siebert, Reiner organization: Institute of Human Genetics, University Hospital Schleswig-Holstein, Campus Kiel/Christian-Albrechts-University Kiel, Germany
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Keywords	Human Prospective Pediatrics Treatment Hematology Lymphoproliferative syndrome Clinical trial Malignant hemopathy B-Lymphocyte Child Lymphoma Cancer
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Snippet	The spectrum of entities, the therapeutic strategy, and the outcome of mature aggressive B-cell non-Hodgkin lymphomas (maB-NHLs) differs between children and...
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SubjectTerms	Adolescent Adult Age Factors Antineoplastic Combined Chemotherapy Protocols - therapeutic use Biological and medical sciences Burkitt Lymphoma - diagnosis Burkitt Lymphoma - genetics Clinical Trials as Topic Female Gene Expression Profiling Hematologic and hematopoietic diseases Humans Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Lymphoma, B-Cell - diagnosis Lymphoma, B-Cell - drug therapy Lymphoma, B-Cell - genetics Lymphoma, Large B-Cell, Diffuse - diagnosis Lymphoma, Large B-Cell, Diffuse - genetics Male Medical sciences Middle Aged Treatment Outcome
Title	Molecular profiling of pediatric mature B-cell lymphoma treated in population-based prospective clinical trials
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