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Gene Expression Profiling and Molecular Diagnosis of B-Cell Lymphomas:

Gene Expression Profiling and Molecular Diagnosis of B-Cell Lymphomas: Towards Clinical Application Andreas Rosenwald, M.D. Institute of Pathology, University of Würzburg, Germany. Gene Expression Profiling Molecular definition of lymphoma subtypes

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Gene Expression Profiling and Molecular Diagnosis of B-Cell Lymphomas:

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  1. Gene Expression Profiling and Molecular Diagnosis of B-Cell Lymphomas: Towards Clinical Application Andreas Rosenwald, M.D. Institute of Pathology, University of Würzburg, Germany

  2. Gene Expression Profiling Molecular definition of lymphoma subtypes Discovery of new molecular lymphoma subtypes Definition of prognostic markers / signatures

  3. Aggressive B-NHL GCB DLBCL ABC DLBCL PMBL Burkitt lymphoma

  4. Gene Expression-based Diagnosis of Lymphoma Lymphoma and Leukemia Molecular Profiling Project (LLMPP), unpublished

  5. Dave et al., Dave et al. NEJM 2006

  6. Application of the mBL signature to the test set of aggressive B-NHL cases (n=110) Test set Training set  Identification of 44 molecular Burkitt lymphoma cases Hummel et al., NEJM 2006

  7. Correlation of the subgroups identified by the mBL signature with morphology

  8. Correlation of the subgroups identified by the mBL signature with immunophenotype

  9. Take Home Messages • Burkitt lymphoma has a distinct gene expression profile. 2. 10-15% disagreement between current diagnosis of BL and the molecular diagnosis using gene expression profiling. 3. Potential over-/undertreatment in some patients with aggressive NHL. 4. DLBCL cases with a MYC break have poor outcome.

  10. Clinical translation – • where do we go from here? • 1. Formalin-fixed and paraffin embedded tissue (FFPE) • Development and validation of immunohistochemical markers • Development of quantitative molecular methods (qRT-PCR) that are applicable in FFPE tissue • Fresh frozen tissue • Development of a diagnostic microarray

  11. Immunohistochemistry Hans algorithm for the distinction of GCB and ABC DLBCL CD10 BCL6 MUM1 GCB / ABC DLBCL

  12. Validation and standardization of immunohistochemical markers in diffuse large B-cell lymphomaA study by the Lunenburg Lymphoma Biomarker Consortium(LLBC) De Jong et al., JCO 2007

  13. LLBCLunenburg Lymphoma Biomarker Consortium • EORTC Daphne de Jong, John Raemaekers, • HOVON Ton Hagenbeek, Amsterdam, the Netherlands • GHGLSG Andreas Rosenwald, Wolfram Klapper, Christoph Thorns, Michael Pfreundschuh • GELA Philippe Gaulard, Thierry Molina, Gilles Salles, • BCCC/ECOG Randy Gascoyne, Mukesh Chhanabhai, Laurie Sehn, Sandra Horning • BNLI Abigail Lee, Andrew Norton; Andrew Lister • NLSG Birgitta Sander, Eva Kimby • Biostatistics Edie Weller, Boston, USA • Advisor Elias Campo

  14. Background • Clinical demand for biomarkers in DLBCL for risk-stratification as a basis for tailored therapy • Increasing numbers of potentially interesting markers available (bcl-2, FoxP1, survivin, Ki-67, GCB/non-GCB etc.) • many published series of DLBCL with remarkably various results

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