Recurrent deletions of the TNFSF7 and TNFSF9 genes in 19p13.3 in diffuse large B-cell and Burkitt lymphomas
René Scholtysik
Institute of Cell Biology (Cancer Research), University of Duisburg-Essen, Medical School, Essen, Germany
Search for more papers by this authorInga Nagel
Institute of Human Genetics, Christian-Albrechts University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
Search for more papers by this authorMarkus Kreuz
Institute of Medical Informatics, Statistics and Epidemiology (IMISE), University of Leipzig, Leipzig, Germany
Search for more papers by this authorInga Vater
Institute of Human Genetics, Christian-Albrechts University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
Search for more papers by this authorMaciej Giefing
Institute of Human Genetics, Christian-Albrechts University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland
Search for more papers by this authorCarsten Schwaenen
Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany
Search for more papers by this authorSwen Wessendorf
Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany
Search for more papers by this authorLorenz Trümper
Department of Hematology/Oncology, University Hospital Göttingen, Göttingen, Germany
Search for more papers by this authorMarkus Loeffler
Institute of Medical Informatics, Statistics and Epidemiology (IMISE), University of Leipzig, Leipzig, Germany
Search for more papers by this authorReiner Siebert
Institute of Human Genetics, Christian-Albrechts University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
Search for more papers by this authorCorresponding Author
Ralf Küppers
Institute of Cell Biology (Cancer Research), University of Duisburg-Essen, Medical School, Essen, Germany
Tel.: 49-201-723-3384, Fax: +49-201-723-3386
Institute of Cell Biology (Cancer Research), University of Duisburg-Essen, Medical School, Virchowstraße 173, D-45122 Essen, GermanySearch for more papers by this authorRené Scholtysik
Institute of Cell Biology (Cancer Research), University of Duisburg-Essen, Medical School, Essen, Germany
Search for more papers by this authorInga Nagel
Institute of Human Genetics, Christian-Albrechts University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
Search for more papers by this authorMarkus Kreuz
Institute of Medical Informatics, Statistics and Epidemiology (IMISE), University of Leipzig, Leipzig, Germany
Search for more papers by this authorInga Vater
Institute of Human Genetics, Christian-Albrechts University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
Search for more papers by this authorMaciej Giefing
Institute of Human Genetics, Christian-Albrechts University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland
Search for more papers by this authorCarsten Schwaenen
Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany
Search for more papers by this authorSwen Wessendorf
Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany
Search for more papers by this authorLorenz Trümper
Department of Hematology/Oncology, University Hospital Göttingen, Göttingen, Germany
Search for more papers by this authorMarkus Loeffler
Institute of Medical Informatics, Statistics and Epidemiology (IMISE), University of Leipzig, Leipzig, Germany
Search for more papers by this authorReiner Siebert
Institute of Human Genetics, Christian-Albrechts University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
Search for more papers by this authorCorresponding Author
Ralf Küppers
Institute of Cell Biology (Cancer Research), University of Duisburg-Essen, Medical School, Essen, Germany
Tel.: 49-201-723-3384, Fax: +49-201-723-3386
Institute of Cell Biology (Cancer Research), University of Duisburg-Essen, Medical School, Virchowstraße 173, D-45122 Essen, GermanySearch for more papers by this authorAbstract
A single nucleotide polymorphism-chip analysis of 98 cases of aggressive B-cell lymphomas revealed a recurrent deletion at 19p13 in nine of the cases. Six further cases with deletions encompassing this region were found in array-comparative genomic hybridization data of 295 aggressive B-cell lymphomas from a previous study. Three cases even showed a homozygous deletion, suggesting a tumor suppressor gene in the deleted region. Two genes encoding members of the tumor necrosis factor superfamily (TNFSF) were located in the minimally deleted region, that is, TNFSF7 and TNFSF9. As no mutations were found within the coding exons of the remaining alleles in the lymphomas with heterozygous deletions, we speculate that the deletions may mostly function through a haploinsufficiency mechanism. The cases with deletions encompassed both diffuse large B-cell lymphomas and Burkitt lymphomas, and a deletion was also found in a Hodgkin lymphoma cell line. Thus, TNFSF7 and TNFSF9 deletions are recurrent genetic lesions in multiple types of human lymphomas.
Supporting Information
Additional Supporting Information may be found in the online version of this article.
| Filename | Description |
|---|---|
| IJC_27416_sm_SuppFig1.tif676.9 KB | Supporting Information Figure 1. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
References
- 1 Swerdlow SH. International Agency for Research on Cancer. WHO classification of tumours of haematopoietic and lymphoid tissues, 4th edn. Lyon, France: International Agency for Research on Cancer, 2008.
- 2 Hartmann EM, Ott G, Rosenwald A. Molecular biology and genetics of lymphomas. Hematol Oncol Clin North Am 2008; 22: 807–23, vii.
- 3 Sweetenham JW. Molecular signatures in the diagnosis and management of diffuse large B-cell lymphoma. Curr Opin Hematol 2011; 18: 288–92.
- 4 Hecht JL, Aster JC. Molecular biology of Burkitt's lymphoma. J Clin Oncol 2000; 18: 3707–21.
- 5 Scholtysik R, Kreuz M, Klapper W, Burkhardt B, Feller AC, Hummel M, Loeffler M, Rosolowski M, Schwaenen C, Spang R, Stein H, Thorns C, et al. Detection of genomic aberrations in molecularly defined Burkitt's lymphoma by array-based, high resolution, single nucleotide polymorphism analysis. Haematologica 2010; 95: 2047–55.
- 6 Hummel M, Bentink S, Berger H, Klapper W, Wessendorf S, Barth TF, Bernd HW, Cogliatti SB, Dierlamm J, Feller AC, Hansmann ML, Haralambieva E, et al. A biologic definition of Burkitt's lymphoma from transcriptional and genomic profiling. N Engl J Med 2006; 354: 2419–30.
- 7 Klapper W, Szczepanowski M, Burkhardt B, Berger H, Rosolowski M, Bentink S, Schwaenen C, Wessendorf S, Spang R, Moller P, Hansmann ML, Bernd HW, et al. Molecular profiling of pediatric mature B-cell lymphoma treated in population-based prospective clinical trials. Blood 2008; 112: 1374–81.
- 8 Schwaenen C, Viardot A, Berger H, Barth TF, Bentink S, Dohner H, Enz M, Feller AC, Hansmann ML, Hummel M, Kestler HA, Klapper W, et al. Microarray-based genomic profiling reveals novel genomic aberrations in follicular lymphoma which associate with patient survival and gene expression status. Genes Chromosomes Cancer 2009; 48: 39–54.
- 9 Kreuz M, Rosolowski M, Berger H, Schwaenen C, Wessendorf S, Loeffler M, Hasenclever D. Development and implementation of an analysis tool for array-based comparative genomic hybridization. Methods Inf Med 2007; 46: 608–13.
- 10 Affymetrix. BRLMM: an improved genotype calling method for the genechip human mapping 500k array set. Technical Report, White Paper. Santa Clara, CA: Affymetrix, 2006.
- 11 Nannya Y, Sanada M, Nakazaki K, Hosoya N, Wang L, Hangaishi A, Kurokawa M, Chiba S, Bailey DK, Kennedy GC, Ogawa S. A robust algorithm for copy number detection using high-density oligonucleotide single nucleotide polymorphism genotyping arrays. Cancer Res 2005; 65: 6071–9.
- 12 Salaverria I, Philipp C, Oschlies I, Kohler CW, Kreuz M, Szczepanowski M, Burkhardt B, Trautmann H, Gesk S, Andrusiewicz M, Berger H, Fey M, et al. Translocations activating IRF4 identify a subtype of germinal center-derived B-cell lymphoma affecting predominantly children and young adults. Blood 2011; 118: 139–47.
- 13 Martin-Subero JI, Harder L, Gesk S, Schlegelberger B, Grote W, Martinez-Climent JA, Dyer MJ, Novo FJ, Calasanz MJ, Siebert R. Interphase FISH assays for the detection of translocations with breakpoints in immunoglobulin light chain loci. Int J Cancer 2002; 98: 470–4.
- 14 Fujita PA, Rhead B, Zweig AS, Hinrichs AS, Karolchik D, Cline MS, Goldman M, Barber GP, Clawson H, Coelho A, Diekhans M, Dreszer TR, et al. The UCSC Genome Browser database: update 2011. Nucleic Acids Res 2010; 39: D876–82.
- 15 Giefing M, Arnemann J, Martin-Subero JI, Nielander I, Bug S, Hartmann S, Arnold N, Tiacci E, Frank M, Hansmann ML, Kuppers R, Siebert R. Identification of candidate tumour suppressor gene loci for Hodgkin and Reed-Sternberg cells by characterisation of homozygous deletions in classical Hodgkin lymphoma cell lines. Br J Haematol 2008; 142: 916–24.
- 16 Berger AH, Knudson AG, Pandolfi PP. A continuum model for tumour suppression. Nature 2011; 476: 163–9.
- 17 Taraban VY, Rowley TF, Tough DF, Al-Shamkhani A. Requirement for CD70 in CD4+ Th cell-dependent and innate receptor-mediated CD8+ T cell priming. J Immunol 2006; 177: 2969–75.
- 18 Laderach D, Wesa A, Galy A. 4-1BB-ligand is regulated on human dendritic cells and induces the production of IL-12. Cell Immunol 2003; 226: 37–44.
- 19 Dolfi DV, Boesteanu AC, Petrovas C, Xia D, Butz EA, Katsikis PD. Late signals from CD27 prevent Fas-dependent apoptosis of primary CD8+ T cells. J Immunol 2008; 180: 2912–21.
- 20 Arens R, Schepers K, Nolte MA, van Oosterwijk MF, van Lier RA, Schumacher TN, van Oers MH. Tumor rejection induced by CD70-mediated quantitative and qualitative effects on effector CD8+ T cell formation. J Exp Med 2004; 199: 1595–605.
- 21 Kim Y, Strehl JW, Gorschluter M, Ziske C, Schmidt-Wolf IG. Prevention of lethal tumor growth and generation of long-lasting immunity in vivo using CD137L and interleukin-12 gene transfer. In Vivo 2008; 22: 337–43.
- 22 Grunebach F, Kayser K, Weck MM, Muller MR, Appel S, Brossart P. Cotransfection of dendritic cells with RNA coding for HER-2/neu and 4-1BBL increases the induction of tumor antigen specific cytotoxic T lymphocytes. Cancer Gene Ther 2005; 12: 749–56.
- 23 Vinay DS, Choi BK, Bae JS, Kim WY, Gebhardt BM, Kwon BS. CD137-deficient mice have reduced NK/NKT cell numbers and function, are resistant to lipopolysaccharide-induced shock syndromes, and have lower IL-4 responses. J Immunol 2004; 173: 4218–29.
- 24 Middendorp S, Xiao Y, Song JY, Peperzak V, Krijger PH, Jacobs H, Borst J. Mice deficient for CD137 ligand are predisposed to develop germinal center-derived B-cell lymphoma. Blood 2009; 114: 2280–9.
- 25 Pasqualucci L, Trifonov V, Fabbri G, Ma J, Rossi D, Chiarenza A, Wells VA, Grunn A, Messina M, Elliot O, Chan J, Bhagat G, et al. Analysis of the coding genome of diffuse large B-cell lymphoma. Nat Genet 2011; 43: 830–7.
Citing Literature
