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Molecular Pathogenesis and Risk Stratification of Lymphoma

Follicular lymphomas (FL) represent, together with diffuse large B cell lymphomas, the most frequent type of malignant lymphomas in Western countries. Biologically, FL represents the neoplastic equivalent of the normal germinal center (GC) reaction, recapitulating the cellular composition of reactive lymphoid follicles. The constitutive overexpression of the anti-apoptotic BCL2-gene inferred by the translocation t(14;18), leads to an accumulation of inappropriately rescued B-cells with a prolonged life span, allowing for the development of additional genetic hits, that are believed to be required for the establishment of FL. These biological features are mirrored in the clinical course of FL, which is highly variable. Some patients present with aggressive disease and die within one year, while others live up to 20 years. Therefore, treatment of follicular lymphoma is one of the most difficult and controversial topics in oncology. It is of major impact, that particularly the expression of genes from non-malignant bystander cells is strongly correlated to the clinical outcome of FL patients, thus revealing an important interplay between the malignant cells and their microenvironment.
Since there is accumulating evidence for the influence of single nucleotide polymorphisms on the prognosis of FL patients, it is highly desirable to characterize prognostically relevant SNPs, originating either from the tumor-relevant genes themselves, or from genes corresponding to the non-malignant bystander cells, to improve the risk-stratification of patients with FL.
 
Major Projects
  • MALDI-TOF MS based screening of single nucleotide polymorphisms (SNPs) in patients with follicular lymphoma
  • Establishment of an ex vivo culture system for follicular lymphoma
  • Gene expression based survival model for patients with follicular lymphoma
  • The role of immunophenotypic variations and genetic/epigenetic alterations in FL and DLBCL patients of the German Low Grade and High Grade Lymphoma Study Groups
Dr. rer. nat. Heike Horn

phone: ++49-711-8101 3712

Selected References
  • Horn H, Pott C, Kalla J, Dreyling M, Rosenwald A, Ott G, Schwab M, Schaeffeler E. A multiplex MALDI-TOF MS approach facilitates genotyping of DNA from formalin-fixed paraffin-embedded tumor specimens. Pharmacogenet Genomics 2010; 20:598-604
  • Ott G, Ziepert M, Klapper W, Horn H, Szczepanowski M, Bernd HW, Thorns C, Feller AC, Lenze D, Hummel M, Stein H, Müller-Hermelink HK, Frank M, Hansmann ML, Barth TFE, Möller P, Cogliatti S, Pfreundschuh M, Schmitz N, Trümper L, Loeffler M, Rosenwald A for the DSHNHL. Immunoblastic morphology but not the immunohistochemical GCB/non-GCB classifier predicts outcome in diffuse large B-cell lymphoma in the RICOVER-60 trial of the DSHNHL. Blood 2010; 116:4916-25
  • Stöcklein H, Smardova J, Macak J, Katzenberger T, Höller S, Wessendorf S, Hutter G, Dreyling M, Haralambieva E, Mäder U, Müller-Hermelink HK, Rosenwald A, Ott G, Kalla J. Detailed mapping of chromosome 17p deletions reveals HIC1 as a novel tumor suppressor gene candidate telomeric to TP53 in diffuse large B-cell lymphoma. Oncogene 2008; 27:2613-25
  • Klapper W, Stoecklein H, Zeynalova S, Ott G, Kosari F, Rosenwald A, Loeffler M, Trümper L, Pfreundschuh M, Siebert R. Structural aberrations affecting the MYC locus indicate a poor prognosis independent of clinical risk factors in diffuse large B-cell lymphomas treated within the randomized trials of the German High-Grade Non-Hodgkin´s Lymphoma Study Group (DSHNHL). Leukemia 2008; 22:2226-29
Major Networks and Collaborations
  • Molecular Mechanisms in Malignant Lymphomas (MMML)
  • German Low Grade Lmyphoma Study Group (GLSG)
Extramural Funding
  • 2004-2006: Graduiertenkolleg 639: ‘Molekulare und Strukturelle Grundlagen der Tumorinstabilität, Julius-Maximilians-University, Würzburg, Germany
  • 2007-2008: Verbundprojekt der Deutschen Krebshilfe/Mildred-Scheel-Stiftung –Molekulare Mechanismen bei malignen Lymphomen Nr. 70-3173-Tr 3 Zentralprojekt A1/Teilprojekt B3/M4 2004-2009
  • 2004-2006: European Proposal No 503351 „European Mantle Cell Lymphoma Network: Translational Determination of Molecular Prognostic Factors“

 

Curriculum Vitae Heike Horn, PhD

Affiliation
Post doctoral scientist
Research Group of the Institute of Pathology, Robert Bosch Hospital

Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology
Auerbachstr. 112
D - 70376 Stuttgart, Germany
phone: ++49-711-8101-3712
fax: ++49-711-85 92 95
email: heike.horn@ikp-stuttgart.de
Education and Professional Career
1999-2004 Study of biology, Julius-Maximilians-University, Würzburg, Germany
2004 Diploma degree for biology
2004-2007 PhD Thesis: ‘Characterization of 17p-deletions in diffuse large B-cell lymphoma and identification of HIC1 as a novel tumor suppressor gene’, Institute of Pathology, Julius-Maximilians-University, Würzburg, Germany
2007 Dr. rer. nat. (PhD) in biology, Julius-Maximilians-University, Würzburg, Germany
2007-2008 Postdoctoral research fellow: Investigation of HIC1 tumor suppressor gene in mantle cell lymphoma. / Molecular characterization of follicular lymphomas. Institute of Pathology, Julius-Maximilians-University, Würzburg, Germany (Head Prof. H.-K. Müller-Hermelink)
01/2008-present Principal Investigator, Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany
Research Group of the Institute of Clinical Pathology, Robert Bosch Hospital, Stuttgart, Germany (Head Prof. G. Ott)