Rainer Spang

About Rainer Spang:

Prof. Dr. Rainer Spang Universität Regensburg Institut für Funktionale Genomik Am BioPark 9 93053 Regensburg

LHA ID: 7WARVMGT27-3

Location:  Germany

ORCID: Not specified

Expertise: Not specified

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MMML Demonstrators - Molecular Mechanisms in Malignant Lymphomas - Demonstrators of Personalized Medicine

The joint project "MMML Demonstrators" deals with improvements in the diagnosis and therapy of lymphoma and consists of seven subprojects. In lymphoma, the so-called diffuse large cell B-cell lymphomas (DLBCL) are responsible for the highest number of deaths. Although the disease is curable in principle, approximately one third of patients still die. However, the expression of certain genes in tumor cells and surrounding tissues can be used to diagnose certain subgroups of these tumors and, in ...

Programme: This Project is not associated with a Programme

Public web page: https://www.sys-med.de/de/demonstratoren/mmml-demonstrators/

Start date: 1st Jan 2015

End date: 31st Dec 2018

GLA - German Lymphoma Alliance: inactive since

B-cell lymphoma is the most frequent lymphoid neoplasia accounting for one third of all lymphomas. R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone) is the current treatment standard, leading to high cure rates especially in younger patients. Although the 3-year event-free survival is about 60% even for elderly patients between 60-80 years old, the remainder of patients eventually relapse and the majority die of their disease. The German Non-Hodgkin's Lymphoma Study ...

Programme: NHL

Public web page: https://www.dshnhl.org

Biological characterization of adult MYC-translocation-positive mature B-cell lymphomas other than molecular Burkitt lymphoma.
MMML - Molecular mechanisms in malignant lymphoma

Abstract (Expand)

Chromosomal translocations affecting the MYC oncogene are the biological hallmark of Burkitt lymphomas but also occur in a subset of other mature B-cell lymphomas. If accompanied by a chromosomal break … targeting the BCL2 and/or BCL6 oncogene these MYC translocation-positive (MYC(+)) lymphomas are called double-hit lymphomas, otherwise the term single-hit lymphomas is applied. In order to characterize the biological features of these MYC(+) lymphomas other than Burkitt lymphoma we explored, after exclusion of molecular Burkitt lymphoma as defined by gene expression profiling, the molecular, pathological and clinical aspects of 80 MYC-translocation-positive lymphomas (31 single-hit, 46 double-hit and 3 MYC(+)-lymphomas with unknown BCL6 status). Comparison of single-hit and double-hit lymphomas revealed no difference in MYC partner (IG/non-IG), genomic complexity, MYC expression or gene expression profile. Double-hit lymphomas more frequently showed a germinal center B-cell-like gene expression profile and had higher IGH and MYC mutation frequencies. Gene expression profiling revealed 130 differentially expressed genes between BCL6(+)/MYC(+) and BCL2(+)/MYC(+) double-hit lymphomas. BCL2(+)/MYC(+) double-hit lymphomas more frequently showed a germinal center B-like gene expression profile. Analysis of all lymphomas according to MYC partner (IG/non-IG) revealed no substantial differences. In this series of lymphomas, in which immunochemotherapy was administered in only a minority of cases, single-hit and double-hit lymphomas had a similar poor outcome in contrast to the outcome of molecular Burkitt lymphoma and lymphomas without the MYC break. Our data suggest that, after excluding molecular Burkitt lymphoma and pediatric cases, MYC(+) lymphomas are biologically quite homogeneous with single-hit and double-hit lymphomas as well as IG-MYC and non-IG-MYC(+) lymphomas sharing various molecular characteristics.

Authors: S. M. Aukema, M. Kreuz, C. W. Kohler, M. Rosolowski, D. Hasenclever, M. Hummel, R. Kuppers, D. Lenze, G. Ott, C. Pott, J. Richter, A. Rosenwald, M. Szczepanowski, C. Schwaenen, H. Stein, H. Trautmann, S. Wessendorf, L. Trumper, M. Loeffler, R. Spang, P. M. Kluin, W. Klapper, R. Siebert

Date Published: 2nd Nov 2013

Publication Type: Not specified

Human Diseases: non-Hodgkin lymphoma, diffuse large B-cell lymphoma

Patient age at diagnosis is associated with the molecular characteristics of diffuse large B-cell lymphoma.
MMML - Molecular mechanisms in malignant lymphoma

Abstract (Expand)

Diffuse large B-cell lymphoma is the most frequent type of B-cell lymphoma in adult patients but also occurs in children. Patients are currently assigned to therapy regimens based on arbitrarily chosen … age limits only (eg, 18 or 60 years) and not biologically justified limits. A total of 364 diffuse large B-cell lymphomas and related mature aggressive B-cell lymphomas other than Burkitt lymphoma from all age groups were analyzed by comprehensive molecular profiling. The probability of several biologic features previously reported to be associated with poor prognosis in diffuse large B-cell lymphoma, such as ABC subtype, BCL2 expression, or cytogenetic complexity, increases with age at diagnosis. Similarly, various genetic features, such as IRF4 translocations, gains in 1q21, 18q21, 7p22, and 7q21, as well as changes in 3q27, including gains and translocations affecting the BCL6 locus, are significantly associated with patient age, but no cut-offs between age groups could be defined. If age was incorporated in multivariate analyses, genetic complexity lost its prognostic significance, whereas the prognostic impact of ABC subtype and age were additive. Our data indicate that aging is a major determinant of lymphoma biology. They challenge current concepts regarding both prognostic biomarkers and treatment stratification based on strict age cut-offs.

Authors: W. Klapper, M. Kreuz, C. W. Kohler, B. Burkhardt, M. Szczepanowski, I. Salaverria, M. Hummel, M. Loeffler, S. Pellissery, W. Woessmann, C. Schwanen, L. Trumper, S. Wessendorf, R. Spang, D. Hasenclever, R. Siebert

Date Published: 23rd Feb 2012

Publication Type: Not specified

Human Diseases: diffuse large B-cell lymphoma

A biologic definition of Burkitt's lymphoma from transcriptional and genomic profiling.
MMML - Molecular mechanisms in malignant lymphoma

Abstract (Expand)

BACKGROUND: The distinction between Burkitt's lymphoma and diffuse large-B-cell lymphoma is unclear. We used transcriptional and genomic profiling to define Burkitt's lymphoma more precisely … and to distinguish subgroups in other types of mature aggressive B-cell lymphomas. METHODS: We performed gene-expression profiling using Affymetrix U133A GeneChips with RNA from 220 mature aggressive B-cell lymphomas, including a core group of 8 Burkitt's lymphomas that met all World Health Organization (WHO) criteria. A molecular signature for Burkitt's lymphoma was generated, and chromosomal abnormalities were detected with interphase fluorescence in situ hybridization and array-based comparative genomic hybridization. RESULTS: We used the molecular signature for Burkitt's lymphoma to identify 44 cases: 11 had the morphologic features of diffuse large-B-cell lymphomas, 4 were unclassifiable mature aggressive B-cell lymphomas, and 29 had a classic or atypical Burkitt's morphologic appearance. Also, five did not have a detectable IG-myc Burkitt's translocation, whereas the others contained an IG-myc fusion, mostly in simple karyotypes. Of the 176 lymphomas without the molecular signature for Burkitt's lymphoma, 155 were diffuse large-B-cell lymphomas. Of these 155 cases, 21 percent had a chromosomal breakpoint at the myc locus associated with complex chromosomal changes and an unfavorable clinical course. CONCLUSIONS: Our molecular definition of Burkitt's lymphoma clarifies and extends the spectrum of the WHO criteria for Burkitt's lymphoma. In mature aggressive B-cell lymphomas without a gene signature for Burkitt's lymphoma, chromosomal breakpoints at the myc locus were associated with an adverse clinical outcome.

Authors: M. Hummel, S. Bentink, H. Berger, W. Klapper, S. Wessendorf, T. F. Barth, H. W. Bernd, S. B. Cogliatti, J. Dierlamm, A. C. Feller, M. L. Hansmann, E. Haralambieva, L. Harder, D. Hasenclever, M. Kuhn, D. Lenze, P. Lichter, J. I. Martin-Subero, P. Moller, H. K. Muller-Hermelink, G. Ott, R. M. Parwaresch, C. Pott, A. Rosenwald, M. Rosolowski, C. Schwaenen, B. Sturzenhofecker, M. Szczepanowski, H. Trautmann, H. H. Wacker, R. Spang, M. Loeffler, L. Trumper, H. Stein, R. Siebert

Date Published: 8th Jun 2006

Publication Type: Not specified

Human Diseases: Burkitt lymphoma

Automated macrophage counting in DLBCL tissue samples: a ROF filter based approach
MMML Demonstrators - Molecular Mechanisms in Malignant Lymphomas - Demonstrators of Personalized Medicine

Abstract (Expand)

We describe a Rudin-Osher-Fatemi (ROF) filter based segmentation approach for whole tissue samples, combining floating intensity thresholding and rule-based feature detection. Method is validated against … manual counts and compared with two commercial software kits (Tissue Studio 64, Definiens AG, and Halo, Indica Labs) and a straightforward machine-learning approach in a set of 50 test images. Further, the novel method and both commercial packages are applied to a set of 44 whole tissue sections. Outputs are compared with gene expression data available for the same tissue samples. Finally, the ROF based method is applied to 44 expert-specified tumor subregions for testing selection and subsampling strategies. Our method is deterministic, fully automated, externally repeatable, independent on training data and -- in difference to most commercial software kits -- completely documented. Among all tested methods, the novel approach is best correlated with manual count (0.9297). Automated detection of evaluation subregions proved to be fully reliable. Subsampling within tumor subregions is possible with results almost identical to full sampling. Comparison with gene expression data obtained for the same tissue samples reveals only moderate to low correlation levels, thus indicating that image morphometry constitutes an independent source of information about antibody-polarized macrophage occurence and distribution.

Authors: Marcus Wagner, René Hänsel, Sarah Reinke, Julia Richter, Michael Altenbuchinger, Ulf-Dietrich Braumann, Rainer Spang, Markus Löffler, Wolfram Klapper

Date Published: No date defined

Publication Type: Not specified

Human Diseases: diffuse large B-cell lymphoma

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