TY - JOUR A1 - Wondergem, Marielle J. A1 - Herrmann, Ken A1 - Syrbu, Sergei A1 - Zijlstra, Josée M. A1 - Hoetjes, Nikie A1 - Hoekstra, Otto S. A1 - Cillessen, Saskia A. G. M. A1 - Moesbergen, Laura M. A1 - Buck, Andreas K. A1 - Vose, Julie M. A1 - Juweid, Malik E. T1 - 18 F-fluorothymidine uptake in follicular lymphoma and error-prone DNA repair JF - EJNMMI Research N2 - BACKGROUND: We observed a disproportional 18 F-fluorothymidine (F-FLT) uptake in follicular lymphoma (FL) relative to its low cell proliferation. We tested the hypothesis that the 'excess' uptake of 18 F-FLT in FL is related to error-prone DNA repair and investigated whether this also contributes to 18 F-FLT uptake in diffuse large B cell lymphoma (DLBCL). METHODS: We performed immunohistochemical stainings to assess the pure DNA replication marker MIB-1 as well as markers of both DNA replication and repair like PCNA, TK-1 and RPA1 on lymph node biopsies of 27 FLs and 35 DLBCLs. In 7 FL and 15 DLBCL patients, 18 F-FLT-PET had been performed. RESULTS: 18 F-FLT uptake was lower in FL than in DLBCL (median SUVmax 5.7 vs. 8.9, p = 0,004), but the ratio of 18 F-FLT-SUVmax to percentage of MIB-1 positive cells was significantly higher in FL compared with DLBCL (p = 0.001). The median percentage of MIB-1 positive cells was 10% (range, 10% to 20%) in FL and 70% (40% to 80%) in DLBCL. In contrast, the median percentages of PCNA, TK-1 and RPA1 positive cells were 90% (range, 80 to 100), 90% (80 to 100) and 100% (80 to 100) in FL versus 90% (60 to 100), 90% (60 to 100) and 100% (80 to 100) in DLBCL, respectively. CONCLUSIONS: This is the first demonstration of a striking discordance between 18 F-FLT uptake in FL and tumour cell proliferation. High expression of DNA replication and repair markers compared with the pure proliferation marker MIB-1 in FL suggests that this discordance might be due to error-prone DNA repair. While DNA repair-related 18 F-FLT uptake considerably contributes to 18 F-FLT uptake in FL, its contribution to 18 F-FLT uptake in highly proliferative DLBCL is small. This apparently high contribution of DNA repair to the 18 F-FLT signal in FL may hamper studies where 18 F-FLT is used to assess response to cytostatic therapy or to distinguish between FL and transformed lymphoma. KW - 18-F-fluorothymidine uptake KW - positron emission tomography KW - follicular lymphoma KW - non-Hodgkin's lymphoma KW - DNA repair Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-121233 VL - 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 -