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Molecular Pathogenesis and Risk Stratification of Lymphoma

"The nature of the surgical pathologist’s work provides privileged insights into human disease and unparalleled opportunities to formulate and test new hypotheses", a quotation from Prof. Peter Isaacson says. As a surgical pathologist and taking advantage of those privileged insights, I am interested in all aspects that are thrown up by the surgical pathology cases. Since it is especially in the field of haematopathology, where morphology meets biology, and where diagnostic work spills out into research, the main interest of my group is to identify biologic features that influence – or are the reason for – morphological traits in hematologic diseases. Malignant lymphoma is a type of disease, in which important aspects of its genetic and epigenetic basis have been identified. Our group has generated novel hypotheses and gained particular insights into the specific clinical behavior of malignant disease. The genesis of both malignant lymphomas and mesotheliomas are intimately associated with impaired cell cycle control, which is one of the hallmarks of cancer. The precise sequel of the events that bring about malignant disease is known in some entities of hematologic neoplasms, but to a far lesser extent in solid tumors. Therefore, with the new pan-genomic analysis tools in identifying, e.g., genetic alterations and altered methylation patterns, we aim at elucidating basic disease principles, their precise role and timing in tumorigenesis, and their impact on the clinical course in an individual patient.
 
Major Projects
  • The role of immunophenotypic variations and genetic/epigenetic alterations in FL and DLBCL tumors of patients treated within studies of the German Low Grade and High Grade Lymphoma Study Groups
  • Genetic and biologic alterations in MCL
  • The role of the Epstein-Barr Virus (EBV) in lympoproliferations of immunosuppressed and immunocompetent patients
  • Gene expression based survival model for patients with follicular lymphoma
  • Genetic polymorphisms in patients with follicular lymphoma
  • Molecular characterization of pleural mesotheliomas: investigation of cell cycle associated proteins in correlation with the status of p16INK4 and p14ARF.
  • Analysis of specific genetic alterations in routine formalin fixed paraffin-embedded tissues as an adjunct in the precise definition of malignant tumors (IZEPHA)
Prof. Dr. German Ott

phone: ++49-711-8101 3390

Selected References
  • Rosenwald A, Wright G, Chan WC, Connors JM, Campo E, Fisher RI, Gascoyne RD, Müller-Hermelink HK, Smeland EB, Giltnane JM, Hurt EM, Zhao H, Averett L, Yang L, Wilson WH, Jaffe ES, Simon R, Klausner RD, Powell J, Duffey PL, Longo DL, Greiner TC, Weisenburger DD, Sanger WG, Dave BJ, lynch JC, Vose J, Armitage JO, Montserrat E, Lopez-Guillermo A, Grogan TM, Miller TP, LeBlanc M, Ott G, Kvaloy S, Delabie J, Holte H, Krajci P, Stokke T, Staudt M; The Lymphoma/Leukemia Profiling Project: The use of molecular profiling to predict survival after chemotherapy for diffuse large B cell lymphoma. N Engl J Med 2002; 346:1937-1947
  • Rosenwald A, Wright G, Wiestner A, Chan WC, Connors JM, Campo E, Gascoyne RD, Grogan TM, Müller-Hermelink HK, Smeland EB, Chiorazzi M, Giltnane JM, Hurt EM, Zhao H, Averett L, Henrickson S, Yang L, Powell J, Wilson WH, Jaffe ES, Simon R, Klausner RD, Montserrat E, Bosch F, Greiner TC, Weisenburger DD, Sanger WG, Dave BJ, Lynch JC, Vose J, Armitage JO, Fisher RI, Miller TP, LeBlanc M, Ott G, Kvaloy S, Holte H, Delabie J, Staudt LM: The proliferation gene expression signature is a quantitative integrator of oncogenic events that predicts survival in mantle cell lymphoma. Cancer Cell 2003; 3:185-197
  • Dave SS, Wright G, Tan B, Rosenwald A, Gascoyne RD, Chan WC, Fisher RI, Braziel RM, Rimsza LM, Grogan TM, Miller TP, LeBlanc M, Greiner TC, Weisenburger DD, Lynch JC, Vose J, Armitage JO, Smeland EB, Kvaloy S, Holte H, Delabie J, Connors JM, Lansdorp PM, Ouyang Q, Lister TA, Davies AJ, Norton AJ, Muller-Hermelink HK, Ott G, Campo E, Montserrat E, Wilson WH, Jaffe ES, Simon R, Yang L, Powell J, Zhao H, Goldschmidt N, Chiorazzi M, Staudt LM. Prediction of survival in follicular lymphoma based on molecular features of tumor-infiltrating immune cells. N Engl J Med 2004; 351:2159-2169
  • Hummel M, Bentink S, Berger H, Klapper W, Wessendorf S, Barth TF, Bernd HW, Cogliatti SB, Dierlamm J, Feller AC, Hansmann ML, Haralambieva E, Harder L, Hasenclever D, Kuhn M, Lenze D, Lichter P, Martin-Subero JI, Moller P, Muller-Hermelink HK, Ott G, Parwaresch RM, Pott C, Rosenwald A, Rosolowski M, Schwaenen C, Sturzenhofecker B, Szczepanowski M, Trautmann H, Wacker HH, Spang R, Loeffler M, Trumper L, Stein H, Siebert R. A biologic definition of Burkitt's lymphoma from transcriptional and genomic profiling. N Engl J Med 2006; 354:2419-2430
  • Dave SS, Fu K, Wright GW, Lam LT, Kluin P, Boerma EJ, Greiner TC, Weisenburger DD, Rosenwald A, Ott G, Muller-Hermelink HK, Gascoyne RD, Delabie J, Rimsza LM, Braziel RM, Grogan TM, Campo E, Jaffe ES, Dave BJ, Sanger W, Bast M, Vose JM, Armitage JO, Connors JM, Smeland EB, Kvaloy S, Holte H, Fisher RI, Miller TP, Montserrat E, Wilson WH, Bahl M, Zhao H, Yang L, Powell J, Simon R, Chan WC, Staudt LM. Molecular diagnosis of Burkitt's lymphoma. N Engl J Med 2006; 354:2431-2442
  • Lenz G, Davis RE, Ngo VN, Lam L, George TC, Wright GW, Dave SS, Zhao H, Xu W, Rosenwald A, Ott G, Muller-Hermelink HK, Gascoyne RD, Connors JM, Rimsza LM, Campo E, Jaffe ES, Delabie J, Smeland EB, Fisher RI, Chan WC, Staudt LM. Oncogenic CARD11 mutations in human diffuse large B cell lymphoma. Science 2008; 319:1676-1679
  • Lenz G, Wright G, Dave SS, Xiao W, Powell J, Zhao H, Xu W, Tan B, Goldschmidt N, Iqbal J, Vose J, Bast M, Fu K, Weisenburger DD, Greiner TC, Armitage JO, Kyle A, May L, Gascoyne RD, Connors JM, Troen G, Holte H, Kvaloy S, Dierickx D, Verhoef G, Delabie J, Smeland EB, Jares P, Martinez A, Lopez-Guillermo A, Montserrat E, Campo E, Braziel RM, Miller TP, Rimsza LM, Cook JR, Pohlman B, Sweetenham J, Tubbs RR, Fisher RI, Hartmann E, Rosenwald A, Ott G, Muller-Hermelink HK, Wrench D, Lister TA, Jaffe ES, Wilson WH, Chan WC, Staudt LM. Stromal gene signatures in large-B-cell lymphomas. N Engl J Med 2008; 359:2313-2323
  • Katzenberger T, Kalla J, Leich E, Stöcklein H, Hartmann E, Barnickel S, Wessendorf S, Ott MM, Müller-Hermelink HK, Rosenwald A, Ott G: A distinctive subtype of t(14;18) negative nodal follicular non-Hodgkin lymphoma characterized by a predominantly diffuse growth pattern and deletions in the chromosomal region 1p36. Blood 2009; 113:1053-61
  • Davis RE, Ngo VN, Lenz G, Tolar P, Young RM, Romesser PB, Kohlhammer H, Lamy L, Zhao H, Yang Y, Xu W, Shaffer AL, Wright G, Xiao W, Powell J, Jiang JK, Thomas CJ, Rosenwald A, Ott G, Muller-Hermelink HK, Gascoyne RD, Connors JM, Johnson NA, Rimsza LM, Campo E, Jaffe ES, Wilson WH, Delabie J, Smeland EB, Fisher RI, Braziel RM, Tubbs RR, Cook JR, Weisenburger DD, Chan WC, Pierce SK, Staudt LM. Chronic active B-cell-receptor signalling in diffuse large B-cell lymphoma. Nature 2010; 463:88-92
  • Ngo VN, Young RM, Schmitz R, Jhavar S, Xiao W, Lim KH, Kohlhammer H, Xu W, Yang Y, Zhao H, Shaffer AL, Romesser P, Wright G, Powell J, Rosenwald A, Muller-Hermelink HK, Ott G, Gascoyne RD, Connors JM, Rimsza LM, Campo E, Jaffe ES, Delabie J, Smeland EB, Fisher RI, Braziel RM, Tubbs RR, Cook JR, Weisenburger DD, Chan WC, Staudt LM. Oncogenically active MYD88 mutations in human lymphoma. Nature. 2011, 470(7332):115-9
  • Rui L, Emre NC, Kruhlak MJ, Chung HJ, Steidl C, Slack G, Wright GW, Lenz G, Ngo VN, Shaffer AL, Xu W, Zhao H, Yang Y, Lamy L, Davis RE, Xiao W, Powell J, Maloney D, Thomas CJ, Möller P, Rosenwald A, Ott G, Muller-Hermelink HK, Savage K, Connors JM, Rimsza LM, Campo E, Jaffe ES, Delabie J, Smeland EB, Weisenburger DD, Chan WC, Gascoyne RD, Levens D, Staudt LM. Cooperative epigenetic modulation by cancer amplicon genes. Cancer Cell. 2010, 18(6):590-605
  • Meyer PN, Fu K, Greiner TC, Smith LM, Delabie J, Gascoyne RD, Ott G, Rosenwald A, Braziel RM, Campo E, Vose JM, Lenz G, Staudt LM, Chan WC, Weisenburger DD. Immunohistochemical methods for predicting cell of origin and survival in patients with diffuse large B-cell lymphoma treated with rituximab. J Clin Oncol. 2011, 29(2):200-7
Major Networks and Collaborations
  • Lymphoma/Leukemia Molecular Profiling Project (LLMPP)
  • Molecular Mechanisms in Malignant Lymphomas (MMML)
  • German Low Grade Lymphoma Study Group (GLSG)
  • German High Grade Lymphoma Study group (GHGLSG)

Curriculum Vitae German Ott, MD

Affiliation
Professor of Pathology
Head, Department of Clinical Pathology Robert Bosch Hospital and
Institute of Pathology University of Würzburg

Robert Bosch Hospital
Auerbachstrasse 110
D - 70376 Stuttgart, Germany
phone: ++49-711-8101-3390
fax: ++49-711-8101-3619
email: german.ott@rbk.de
Education and Professional Career
1988-1990 Postdoctoral Fellow at the Department of Pathology, Technical University of Aachen, Germany
1990-1998 Postdoctoral Fellow and Pathologist in training at the Institute of Pathology, University of Würzburg, Germany
1998-2006 Staff Pathologist and Associate Professor at the Institute of Pathology, University of Würzburg, Germany
2006-2007 Full Professor, Cytopathology and Tumor Genetics at the Institute of Pathology, University of Würzburg, Germany
4/2007-present Professor of Pathology, Head of the Department of Clinical Pathology, Robert-Bosch Krankenhaus, Stuttgart, Germany
Professional Memberships
European Association of Haematopathology
Berufsverband Pathologie
International Academy of Pathology
Scientific Journal Editorial Board Memberships
Annals of Hematology
Journal of Haematopathology
Journal of Clinical Oncology