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Project R

Project R

 

 

Name:

Prof. Dr. Brigitte Schlegelberger

 

Institution:

Institute of Cell- and Molecular Pathology

 

Telephone:

0049-511-532-4522

 

Email:

Schlegelberger.Brigittemh-hannover.de

 

Research focus:

Characterization of Molecular and Biological Risk Factors in Mantle Cell Lymphomas

 

Mantle cell lymphomas derived from naive B-cells and have an aggressive clinical course with a median survival of about 3 years. The cytogenetic hallmark of mantle cell lymphomas (MCL) is the translocation t(11;14)(q13;q32). At the molecular level, the t(11;14) juxtaposes the BCL1-locus in chromosome band 11q13 next to the immunoglobulin heavy chain (IgH) locus in chromosome band 14q32, resulting in overexpression of the cell cycle regulator cyclin D1 (CCND1). Cyclin D1 protein plays a crucial role in cell cycle progression by promoting the G1-S phase transition. Though overexpression of CCND1 due to the t(11;14) is regarded as the primary event in the pathogenesis of mantle cell lymphomas, experimental data from transgenic mice suggest that cyclin D1 has minimal oncogenic potential, being insufficient to induce tumorigenicity by itself. Thus, the acquisition of secondary genetic changes appears to be crucial for the malignant transformation and clonal progression of CCND1-overexpressing lymphocytes.

 

Group members:

Dr. Doris Steinemann

Dr. Nils von Neuhoff

Jennifer Espenkötter, Ella Kammerer (technicians)

 

Methods:

Isolation of DNA and RNA from cells and tissues

c-DNA Synthesis

Quantitative RT-PCR

Quantitative Microsatellite analysis

Fluorescence in situ hybridazation

Mutation analysis by SSCP and sequencing

Methylation specific PCR

c-DNA-Microarrays and Matrix CGH (Comparative genomic hybridization)

Cell culture

Microdissection of cells from paraffin sections

Chromosome analysis

Comparative hybridization

 

Key References:

Zhang Q, Siebert R, Yan M, Hinzmann B, Cui X, Xue L, Rakestraw KM, Naeve CW, Beckmann G, Weisenburger DD, Sanger WG, Nowotny H, Vesely M, Callet-Bauchu E, Salles G, Dixit VM, Rosenthal A, Schlegelberger B, Morris SW. Inactivating mutations and overexpression of BCL10, a caspase recruitment domain-containing gene, in MALT lymphoma with t(1;14)(p22;q32). Nat.Genet. 1999;22:63-68

 

Bea S, Ribas M, Hernandez JM, Bosch F, Pinyol M, Hernandez L, Garcia JL, Flores T, Gonzalez M, Lopez-Guillermo A, Piris MA, Cardesa A, Montserrat E, Miro R, Campo E. Increased number of chromosomal imbalances and high-level DNA amplifications in mantle cell lymphoma are associated with blastoid variants. Blood 1999;93:4365-4374

 

Schlegelberger B, Zwingers T, Harder L, Nowotny H, Siebert R, Vesely M, Bartels H, Sonnen R, Hopfinger G, Nader A, Ott G, Muller-Hermelink K, Feller A, Heinz R. Clinicopathogenetic significance of chromosomal abnormalities in patients with blastic peripheral B-cell lymphoma. Kiel-Wien-Lymphoma Study Group. Blood 1999;94: 3114-3120

 

Steinemann D, Siebert R, Harder S, Martin-Subero I, Kettwig G, Hinzmann B, Gesk S, Tiemann M, Merz H, Rosenthal A, Grote W, Morris SW, Schlegelberger B: Frequent allelic loss of the BCL10 gene in lymphomas with the t(11;14)(q13;q32). Leukemia 2001;15: 474-475

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