Genomic DNA-chip hybridization in t(11;14)-positive mantle cell lymphomas shows a high frequency of aberrations and allows a refined characterization of consensus regions

Author:

Kohlhammer Holger1,Schwaenen Carsten1,Wessendorf Swen1,Holzmann Karlheinz1,Kestler Hans A.1,Kienle Dirk1,Barth Thomas F. E.1,Möller Peter1,Ott German1,Kalla Jörg1,Radlwimmer Bernhard1,Pscherer Armin1,Stilgenbauer Stephan1,Döhner Hartmut1,Lichter Peter1,Bentz Martin1

Affiliation:

1. From the Departments of Innere Medizin I and Innere Medizin III, Medizinische Klinik der Universität Ulm, Ulm, Germany; Departments of Neuroinformatik and Pathologie, Universität Ulm, Ulm, Germany; Department of Pathologie, Universität Würzburg, Würzburg, Germany; and Department of Molekulare Genetik, Deutsches Krebsforschungszentrum, Heidelberg, Germany.

Abstract

AbstractTumor samples of 53 patients with t(11;14)-positive mantle cell lymphomas (MCLs) were analyzed by matrix-based comparative genomic hybridization (matrix-CGH) using a dedicated DNA array. In 49 cases, genomic aberrations were identified. In comparison to chromosomal CGH, a 50% higher number of aberrations was found and the high specificity of matrix-CGH was demonstrated by fluorescence in situ hybridization (FISH) analyses. The 11q gains and 13q34 deletions, which have not been described as frequent genomic aberrations in MCL, were identified by matrix-CGH in 15 and 26 cases, respectively. For several genomic aberrations, novel consensus regions were defined: 8p21 (size of the consensus region, 2.4 megabase pairs [Mbp]; candidate genes: TNFRSF10B, TNFRSF10C, TNFRSF10D); 10p13 (2.7 Mbp; BMI1); 11q13 (1.4 Mbp; RELA); 11q13 (5.2 Mbp; CCND1); 13q14 (0.4 Mbp; RFP2, BCMSUN) and 13q34 (6.9 Mbp). In univariate analyses correlating genomic aberrations and clinical course, 8p- and 13q14- deletions were associated with an inferior overall survival. These data provide a basis for further studies focusing on the identification of pathogenetically or clinically relevant genes in MCL.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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