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Katja Maurus, Silke Appenzeller, Sabine Roth, Jochen Kuper, Simone Rost, Svenja Meierjohann, Panagiota Arampatzi, Matthias Goebeler, Andreas Rosenwald, Eva Geissinger, Marion Wobser
Primary cutaneous marginal zone lymphoma (PCMZL) represents an indolent subtype of Non-Hodgkin lymphomas being clinically characterized by slowly growing tumors of the skin, but a very low propensity for systemic dissemination. Up to now, the underlying genetic basis of PCMZL has not been comprehensively elucidated. With the aim to gain deeper insight into the molecular pathogenesis of PCMZL, we performed hybridization-based panel sequencing of 38 cases of well-characterized PCMZL. In 32 out of 38 cases we identified genetic alterations within 39 selected target genes...
February 23, 2018: Journal of Investigative Dermatology
David W Scott, Rebecca L King, Annette M Staiger, Susana Ben-Neriah, Aixiang Jiang, Heike Horn, Anja Mottok, Pedro Farinha, Graham W Slack, Daisuke Ennishi, Norbert Schmitz, Michael Pfreundschuh, Grzegorz S Nowakowski, Brad S Kahl, Joseph M Connors, Randy D Gascoyne, German Ott, William R Macon, Andreas Rosenwald
High grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements (HGBL-DH/TH) is a newly defined entity in the latest World Health Organization Classification. Accurate diagnosis would appear to mandate fluorescence in situ hybridization (FISH) for all tumors with diffuse large B-cell lymphoma (DLBCL) morphology. We present the results of FISH, cell-of-origin and immunohistochemistry (IHC) testing from 1228 DLBCL biopsies from three clinical trials and a population-based registry. HGBL-DH/TH made up 7...
February 23, 2018: Blood
Nicola Mulder, Russell Schwartz, Michelle D Brazas, Cath Brooksbank, Bruno Gaeta, Sarah L Morgan, Mark A Pauley, Anne Rosenwald, Gabriella Rustici, Michael Sierk, Tandy Warnow, Lonnie Welch
Bioinformatics is recognized as part of the essential knowledge base of numerous career paths in biomedical research and healthcare. However, there is little agreement in the field over what that knowledge entails or how best to provide it. These disagreements are compounded by the wide range of populations in need of bioinformatics training, with divergent prior backgrounds and intended application areas. The Curriculum Task Force of the International Society of Computational Biology (ISCB) Education Committee has sought to provide a framework for training needs and curricula in terms of a set of bioinformatics core competencies that cut across many user personas and training programs...
February 2018: PLoS Computational Biology
Hilka Rauert-Wunderlich, Martina Rudelius, Ingolf Berberich, Andreas Rosenwald
Drug resistance is a significant obstacle in cancer treatment and therefore a frequent subject of research. Developed or primary resistance limits the treatment success of inhibitors of the B cell receptor (BCR) pathway in mantle cell lymphoma (MCL) patients. Recent research has highlighted the role of the nuclear factor-kappa B (NFκB) pathway in the context of resistance to BCR inhibitors in MCL. In this study, we analyzed the dependency of MCL cell lines on NFκB signaling and illustrated the ability of CD40L to activate the alternative NFκB pathway in MCL...
January 24, 2018: Cell Death & Disease
Robert S Ohgami, Andreas Rosenwald, Adam Bagg
This commentary highlights the article by Hung et al that details the design and implementation of a 32-gene next-generation sequencing (NGS) panel for lymphomas, and compares hybrid-capture versus amplicon-based NGS approaches.
January 18, 2018: Journal of Molecular Diagnostics: JMD
David Lasar, Matthias Rosenwald, Elke Kiehlmann, Miroslav Balaz, Bettina Tall, Lennart Opitz, Martin E Lidell, Nicola Zamboni, Petra Krznar, Wenfei Sun, Lukas Varga, Patrik Stefanicka, Jozef Ukropec, Pirjo Nuutila, Kirsi Virtanen, Ez-Zoubir Amri, Sven Enerbäck, Walter Wahli, Christian Wolfrum
Peroxisome proliferator-activated receptors (PPARs) have been suggested as the master regulators of adipose tissue formation. However, their role in regulating brown fat functionality has not been resolved. To address this question, we generated mice with inducible brown fat-specific deletions of PPARα, β/δ, and γ, respectively. We found that both PPARα and β/δδ are dispensable for brown fat function. In contrast, we could show that ablation of PPARγ in vitro and in vivo led to a reduced thermogenic capacity accompanied by a loss of inducibility by β-adrenergic signaling, as well as a shift from oxidative fatty acid metabolism to glucose utilization...
January 16, 2018: Cell Reports
B Glass, A J Dohm, L H Truemper, M Pfreundschuh, A Bleckmann, G G Wulf, A Rosenwald, M Ziepert, N Schmitz
Background: The prognosis of elderly patients with aggressive B-non-Hodgkin's lymphoma after first lymphoma-related treatment failure (TF-L) is not well described. Methods: We analysed patient characteristics including the presence of MYC rearrangements and MYC-expression immunohistochemistry (IHC) at diagnosis and modalities of salvage therapy and their impact on the prognosis of patients between 61 and 80 years who had been treated on the RICOVER-60 trial. Results: TF-L occurred in 301 of the 1222 (24...
December 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Constantin Lapa, Stefan Kircher, Andreas Schirbel, Andreas Rosenwald, Saskia Kropf, Theo Pelzer, Thorsten Walles, Andreas K Buck, Wolfgang A Weber, Hans-Juergen Wester, Ken Herrmann, Katharina Lückerath
C-X-C motif chemokine receptor 4 (CXCR4) is a key factor for tumor growth and metastasis in several types of human cancer. This study investigated the feasibility of CXCR4-directed imaging with positron emission tomography/computed tomography (PET/CT) using [68 Ga]Pentixafor in malignant pleural mesothelioma. Six patients with pleural mesothelioma underwent [68 Ga]Pentixafor-PET/CT. 2'-[18 F]fluoro-2'-deoxy-D-glucose ([18 F]FDG)-PET/CT (4/6 patients) and immunohistochemistry obtained from biopsy or surgery (all) served as standards of reference...
November 14, 2017: Oncotarget
Sietse M Aukema, Eva Hoster, Andreas Rosenwald, Danielle Canoni, Marie-Hélène Delfau-Larue, Grzegorz Rymkiewicz, Christoph Thorns, Sylvia Hartmann, Hanneke Kluin-Nelemans, Olivier Hermine, Martin Dreyling, Wolfram Klapper
Currently, prediction of time to treatment failure (TTF) and overall survival (OS) in mantle cell lymphoma (MCL) is based on the clinical factors included in the Mantle Cell Lymphoma International Prognostic Index (MIPI), and proliferation is assessed by Ki67. However, TP53 and SOX11 immunohistochemistry might improve risk stratification. We performed SOX11 and TP53 immunohistochemistry on the so far largest published cohort of lymphoma specimens (n = 365). All patients were treated in prospective trials of the European MCL Network...
January 25, 2018: Blood
Alberto Zamò, Jordan Pischimarov, Heike Horn, German Ott, Andreas Rosenwald, Ellen Leich
Predominantly diffuse t(14;18) negative follicular lymphoma (FL) with 1p36 deletion shows distinctive clinical, morphological and molecular features that distinguish it from classical FL. In order to investigate whether it possesses a unique mutation profile, we performed whole exome sequencing of six well-characterised cases. Our analysis showed that the mutational landscape of this subtype is largely distinct from classical FL. It appears to harbour several recurrent mutations, affecting STAT6, CREBBP and basal membrane protein genes with high frequency...
February 2018: British Journal of Haematology
Valeria Laufs, Barbara Altieri, Silviu Sbiera, Stefan Kircher, Sonja Steinhauer, Felix Beuschlein, Marcus Quinkler, Holger S Willenberg, Andreas Rosenwald, Martin Fassnacht, Cristina L Ronchi
OBJECTIVE: Platinum-based chemotherapy (PBC) is the most effective cytotoxic treatment for advanced adrenocortical carcinoma (ACC). Excision repair cross complementing group 1 (ERCC1) plays a critical role in the repair of platinum-induced DNA damage. Two studies investigating the role of ERCC1 immunostaining as a predictive marker for the response to PBC in ACC had reported conflicting results. Both studies used the ERCC1-antibody clone 8F1 that later turned out to be not specific. The aim of this study was to evaluate the predictive role of ERCC1 with a new specific antibody in a larger series of ACC...
February 2018: European Journal of Endocrinology
Anja Mottok, Vindi Jurinovic, Pedro Farinha, Andreas Rosenwald, Ellen Leich, German Ott, Heike Horn, Wolfram Klapper, Michael Boesl, Wolfgang Hiddemann, Christian Steidl, Joseph M Connors, Laurie H Sehn, Randy D Gascoyne, Eva Hoster, Oliver Weigert, Robert Kridel
Follicular lymphoma (FL) is a clinically and molecularly highly heterogeneous disease, yet prognostication relies predominantly on clinical tools. We recently demonstrated that integration of mutation status of seven genes, including EZH2 and MEF2B, improves risk stratification. We mined gene expression data to uncover genes that are differentially expressed in EZH2- and MEF2B-mutated cases. We focused on FOXP1 and assessed its protein expression by immunohistochemistry (IHC) in a total of 763 tissue biopsies...
November 9, 2017: Blood
Judith E K Henning, Timo Deutschbein, Barbara Altieri, Sonja Steinhauer, Stefan Kircher, Silviu Sbiera, Vanessa Wild, Wiebke Schlötelburg, Matthias Kroiss, Paola Perotti, Andreas Rosenwald, Alfredo Berruti, Martin Fassnacht, Cristina L Ronchi
Context: Adrenocortical carcinoma (ACC) is rare and confers an unfavorable prognosis in advanced stages. Other than combination chemotherapy with cisplatin, etoposide, doxorubicin, and mitotane, the second- and third-line regimens are not well-established. Gemcitabine (GEM)-based chemotherapy was suggested in a phase 2 clinical trial with 28 patients. In other solid tumors, human equilibrative nucleoside transporter type 1 (hENT1) and/or ribonucleotide reductase catalytic subunit M1 (RRM1) expression have been associated with resistance to GEM...
November 1, 2017: Journal of Clinical Endocrinology and Metabolism
Martina Rudelius, Mathias Tillmann Rosenfeldt, Ellen Leich, Hilka Rauert-Wunderlich, Antonio Giovanni Solimando, Andreas Beilhack, German Ott, Andreas Rosenwald
Mantle cell lymphoma and other lymphoma subtypes often spread to the bone marrow, and stromal interactions mediated by focal adhesion kinase frequently enhance survival and drug resistance of the lymphoma cells. To study the role of focal adhesion kinase in mantle cell lymphoma, immunohistochemistry of primary cases and functional analysis of mantle cell lymphoma cell lines and primary mantle cell lymphoma cells cocultured with bone marrow stromal cells (BMSC) using small molecule inhibitors and RNAi based focal adhesion kinase silencing was performed...
October 27, 2017: Haematologica
A G Solimando, A Brandl, K Mattenheimer, C Graf, M Ritz, A Ruckdeschel, T Stühmer, Z Mokhtari, M Rudelius, J Dotterweich, M Bittrich, V Desantis, R Ebert, P Trerotoli, M A Frassanito, A Rosenwald, A Vacca, H Einsele, F Jakob, A Beilhack
Cell adhesion in the multiple myeloma (MM) microenvironment has been recognized as a major mechanism of MM cell survival and the development of drug resistance. Here we addressed the hypothesis that the protein junctional adhesion molecule-A (JAM-A) may represent a novel target and a clinical biomarker in MM. We evaluated JAM-A expression in MM cell lines and in 147 MM patient bone marrow aspirates and biopsies at different disease stages. Elevated JAM-A levels in patient-derived plasma cells were correlated with poor prognosis...
September 28, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Grit Mutzbauer, Katja Maurus, Clara Buszello, Jordan Pischimarov, Sabine Roth, Andreas Rosenwald, Andreas Chott, Eva Geissinger
Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), formerly known as type II enteropathy associated T-cell lymphoma (type II EATL), is a rare, aggressive primary intestinal T-cell lymphoma with a poor prognosis and an incompletely understood pathogenesis. We collected 40 cases of MEITL and 27 cases of EATL, formerly known as type I EATL, and comparatively investigated the T-cell receptor (TCR) itself and associated signaling molecules using immunohistochemistry, amplicon deep sequencing and bisulfite pyrosequencing...
October 20, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
Martina Rudelius, Klaus Brehm, Martin Poelcher, Christoph Spinner, Andreas Rosenwald, Clarissa Prazeres da Costa
Introduction. Correct diagnosis of peritoneal infectious disease can be extremely difficult due to non-specific clinical features. Thus, careful assessment with thorough histopathological work-up is essential. Here, we report the first case of human peritoneal cysticercosis mimicking peritoneal carcinosis. Case presentation. The patient presented with recurring ascites and a tumour in the Douglas cavity accompanied by elevated tumour markers. There were no signs of systemic infection. On laparoscopy, the tumour was resected completely...
June 2017: JMM Case Reports
Lisa Rimsza, Stefania Pittaluga, Stephan Dirnhofer, Christiane Copie-Bergman, Laurence de Leval, Fabio Facchetti, Stefano Pileri, Andreas Rosenwald, Andrew Wotherspoon, Falko Fend
Our understanding of mature aggressive B cell lymphomas has evolved significantly in the last years as reflected in the 2016 update of the WHO lymphoma classification. A main topic of the 2016 European Association for Haematopathology/Society of Hematopathology lymphoma workshop in Basel therefore was the clinicopathological spectrum of mature aggressive B cell lymphomas with the exception of conventional diffuse large B cell lymphoma. In this review, we summarize two sessions dedicated to "high-grade B cell lymphomas, with MYC and BCL2 and/or BCL6 rearrangements (so-called double/triple-hit lymphomas)" and "high-grade B cell lymphomas, NOS" as defined in the 2016 update of the WHO lymphoma classification, Burkitt lymphoma and related neoplasms, and terminally differentiated aggressive B cell lymphomas...
October 2017: Virchows Archiv: An International Journal of Pathology
Ulrike Paul, Julia Richter, Christiane Stuhlmann-Laiesz, Markus Kreuz, Inga Nagel, Heike Horn, Annette M Staiger, Sietse M Aukema, Michael Hummel, German Ott, Rainer Spang, Andreas Rosenwald, Alfred C Feller, Sergio Cogliatti, Harald Stein, Martin-Leo Hansmann, Peter Moller, Monika Szczepanowski, Birgit Burkhardt, Michael Pfreundschuh, Norbert Schmitz, Markus Loeffler, Lorenz Trümper, Reiner Siebert, Wolfram Klapper
The incidence of diffuse large B-cell lymphoma (DLBCL) increases with age being patient age at diagnosis an adverse prognostic factor. However, elderly patients are often underrepresented in common studies. To investigate the effect between age and biological characteristics in DLBCL, we analyzed data of 1534 patients encompassing all adult age groups, enriched for the age ≥75 years. Follicular lymphoma (FL) grade 3B with histopathological characteristics of DLBCLs were included. Gender, centroblastic cytology, FL grade 3B morphology, CD10 expression, and ABC/non-GCB-subtype were significantly associated with age after correction for multiple testing and after adjusting for cohorts...
May 2018: Leukemia & Lymphoma
Alyssa Bouska, Chengfeng Bi, Waseem Lone, Weiwei Zhang, Ambreen Kedwaii, Tayla Heavican, Cynthia M Lachel, Jiayu Yu, Roberto Ferro, Nanees Eldorghamy, Timothy C Greiner, Julie Vose, Dennis D Weisenburger, Randy D Gascoyne, Andreas Rosenwald, German Ott, Elias Campo, Lisa M Rimsza, Elaine S Jaffe, Rita M Braziel, Reiner Siebert, Rodney R Miles, Sandeep Dave, Anupama Reddy, Jan Delabie, Louis M Staudt, Joo Y Song, Timothy W McKeithan, Kai Fu, Michael Green, Wing C Chan, Javeed Iqbal
The adult high-grade B-cell lymphomas sharing molecular features with Burkitt lymphoma (BL) are highly aggressive lymphomas with poor clinical outcome. High-resolution structural and functional genomic analysis of adult Burkitt lymphoma (BL) and high-grade B-cell lymphoma with BL gene signature (adult-molecularly defined BL [mBL]) revealed the MYC-ARF-p53 axis as the primary deregulated pathway. Adult-mBL had either unique or more frequent genomic aberrations (del13q14, del17p, gain8q24, and gain18q21) compared with pediatric-mBL, but shared commonly mutated genes...
October 19, 2017: Blood
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