TY  - JOUR
A1  - Horn, Heike
A1  - Bausinger, Julia
A1  - Staiger, Annette M.
A1  - Sohn, Maximilian
A1  - Schmelter, Christopher
A1  - Gruber, Kim
A1  - Kalla, Claudia
A1  - Ott, M. Michaela
A1  - Rosenwald, Andreas
A1  - Ott, German
T1  - Numerical and Structural Genomic Aberrations Are Reliably Detectable in Tissue Microarrays of Formalin-Fixed Paraffin-Embedded Tumor Samples by Fluorescence In-Situ Hybridization
JF  - PLOS ONE
N2  - Few data are available regarding the reliability of fluorescence in-situ hybridization (FISH), especially for chromosomal deletions, in high-throughput settings using tissue microarrays (TMAs). We performed a comprehensive FISH study for the detection of chromosomal translocations and deletions in formalin-fixed and paraffin-embedded (FFPE) tumor specimens arranged in TMA format. We analyzed 46 B-cell lymphoma (B-NHL) specimens with known karyotypes for translocations of IGH-, BCL2-, BCL6- and MYC-genes. Locus-specific DNA probes were used for the detection of deletions in chromosome bands 6q21 and 9p21 in 62 follicular lymphomas (FL) and six malignant mesothelioma (MM) samples, respectively. To test for aberrant signals generated by truncation of nuclei following sectioning of FFPE tissue samples, cell line dilutions with 9p21-deletions were embedded into paraffin blocks. The overall TMA hybridization efficiency was 94%. FISH results regarding translocations matched karyotyping data in 93%. As for chromosomal deletions, sectioning artefacts occurred in 17% to 25% of cells, suggesting that the proportion of cells showing deletions should exceed 25% to be reliably detectable. In conclusion, FISH represents a robust tool for the detection of structural as well as numerical aberrations in FFPE tissue samples in a TMA-based high-throughput setting, when rigorous cut-off values and appropriate controls are maintained, and, of note, was superior to quantitative PCR approaches.
KW  - mantel cell lymphoma
KW  - amplifications
KW  - abnormalities
KW  - deletions
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-116706
SN  - 1932-6203
VL  - 9
IS  - 4
ER  - 
TY  - JOUR
A1  - Aukema, Sietse M.
A1  - Kreuz, Markus
A1  - Kohler, Christian W.
A1  - Rosolowski, Maciej
A1  - Hasenclever, Dirk
A1  - Hummel, Michael
A1  - Küppers, Ralf
A1  - Lenze, Diddo
A1  - Ott, German
A1  - Pott, Christiane
A1  - Richter, Julia
A1  - Rosenwald, Andreas
A1  - Szczepanowski, Monika
A1  - Schwaenen, Carsten
A1  - Stein, Harald
A1  - Trautmann, Heiko
A1  - Wessendorf, Swen
A1  - Trümper, Lorenz
A1  - Loeffler, Markus
A1  - Spang, Rainer
A1  - Kluin, Philip M.
A1  - Klapper, Wolfram
A1  - Siebert, Reiner
T1  - Biological characterization of adult MYC-translocation-positive mature B-cell lymphomas other than molecular Burkitt lymphoma
JF  - Haematologica
N2  - 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.
KW  - Rituximab plus
KW  - cyclophsophamide
KW  - c-myc
KW  - gene expression
KW  - genomic aberrations
KW  - follicular lymphoma
KW  - prognostic factor
KW  - poor prognosis
KW  - grade 3B
KW  - distinct
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-116882
SN  - 1592-8721
VL  - 99
IS  - 4
ER  -