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Genomic lymphoma

Nathan D Montgomery, Wilborn B Coward, Steven Johnson, Ji Yuan, Margaret L Gulley, Stephanie P Mathews, Kathleen Kaiser-Rogers, Kathleen W Rao, Warren G Sanger, Jennifer N Sanmann, Yuri Fedoriw
Classical Hodgkin lymphoma (CHL) is morphologically characterized by scattered malignant Hodgkin/Reed-Sternberg (HRS) cells that are far outnumbered by surrounding reactive hematolymphoid cells. Approximately half of all cases of CHL are associated with infection by Epstein-Barr virus (EBV), an oncogenic herpesvirus that expresses a number of proteins thought to contribute to transformation. While a small number of published studies have attempted to identify recurrent cytogenetic abnormalities in CHL, no large case series have explored karyotypic differences between EBV-positive and EBV-negative tumors...
September 2016: Cancer Genetics
Clémentine Sarkozy, Sophie Kaltenbach, Pierre Faurie, Danielle Canioni, Françoise Berger, Alexandra Traverse-Glehen, Hervé Ghesquieres, Gilles Salles, Emmanuel Bachy, Marie-Alexandra Alyanakian, Olivier Hermine, Bénédicte Neven, Elizabeth Macintyre, Serge Romana, Thierry Jo Molina, Felipe Suarez, Vahid Asnafi, Julie Bruneau
Plasma-cell post-transplantation lymphoproliferative disorder (PC-PTLD) is a rare monomorphic PTLD entity divided into plasma cell myeloma (PCM) and plasmacytoma-like lesion (PLL) PTLD. To date, there are no exhaustive published cytogenetic data on PC-PTLD. We report array-based comparative genomic hybridization (aCGH) of 10 cases of PCM and PLL-PTLD. Patients had received kidney (n=6), heart (n=2), lung (n=1) or bone marrow (n=1) transplantation. There were six men and median age at time of PTLD was 56.5 years (3-74)...
October 17, 2016: Genes, Chromosomes & Cancer
Linda M Slot, Robbert Hoogeboom, Laura A Smit, Thera A M Wormhoudt, Bart J Biemond, Monique E C M Oud, Esther J M Schilder-Tol, André B Mulder, Aldo Jongejan, Antoine H C van Kampen, Philip M Kluin, Jeroen E J Guikema, Richard J Bende, Carel J M van Noesel
Follicular lymphoma (FL) is an indolent B-cell non-Hodgkin lymphoma able to transform into germinal center-type diffuse large B-cell lymphoma. We describe four extraordinary cases of FL, which progressed to TdT(+)CD20(-) precursor B-lymphoblastic lymphoma (B-LBL). Fluorescence in situ hybridization analysis showed that all four B-LBLs had acquired a MYC translocation on transformation. Comparative genomic hybridization analysis of one case demonstrated that in addition to 26 numerical aberrations that were shared between the FL and B-LBL, deletion of CDKN2A/B and 17q11, 14q32 amplification, and copy-neutral loss of heterozygosity of 9p were gained in the B-LBL cells...
October 14, 2016: American Journal of Pathology
Jessica Woodward, Gillian C Taylor, Dinesh C Soares, Shelagh Boyle, Daoud Sie, David Read, Keerthi Chathoth, Milica Vukovic, Nuria Tarrats, David Jamieson, Kirsteen J Campbell, Karen Blyth, Juan Carlos Acosta, Bauke Ylstra, Mark J Arends, Kamil R Kranc, Andrew P Jackson, Wendy A Bickmore, Andrew J Wood
Chromosomal instability is a hallmark of cancer, but mitotic regulators are rarely mutated in tumors. Mutations in the condensin complexes, which restructure chromosomes to facilitate segregation during mitosis, are significantly enriched in cancer genomes, but experimental evidence implicating condensin dysfunction in tumorigenesis is lacking. We report that mice inheriting missense mutations in a condensin II subunit (Caph2(nes)) develop T-cell lymphoma. Before tumors develop, we found that the same Caph2 mutation impairs ploidy maintenance to a different extent in different hematopoietic cell types, with ploidy most severely perturbed at the CD4(+)CD8(+) T-cell stage from which tumors initiate...
October 13, 2016: Genes & Development
Miyeon Cho, Seok Won Jung, Soomin Lee, Kuwon Son, Gyu Hwan Park, Jong-Wha Jung, Yu Su Shin, Taegun Seo, Hyosun Cho, Hyojeung Kang
Kaposi's sarcoma-associated herpesvirus (KSHV) is a Gammaherpesvirus that causes acute infection and establishes life-long latency. KSHV causes several human cancers, including Kaposi's sarcoma, an acquired immune deficiency syndrome (AIDS)-related form of non-Hodgkin lymphoma. Genipin, an aglycone derived from geniposide found in Gardenia jasminoides, is known to be an excellent natural cross-linker, strong apoptosis inducer, and antiviral agent. Although evidence suggests antiviral activity of genipin in several in vitro viral infection systems, no inhibitory effect of genipin on KSHV infection has been reported...
2016: PloS One
Atish Mohanty, Natalie Sandoval, Manasi Das, Raju Pillai, Lu Chen, Robert W Chen, Hesham M Amin, Michael Wang, Guido Marcucci, Dennis D Weisenburger, Steven T Rosen, Lan V Pham, Vu N Ngo
Mantle cell lymphoma (MCL) is characterized by the t(11;14) translocation, which leads to deregulated expression of the cell cycle regulatory protein cyclin D1 (CCND1). Genomic studies of MCL have also identified recurrent mutations in the coding region of CCND1. However, the functional consequence of these mutations is not known. Here, we showed that, compared to wild type (WT), single E36K, Y44D or C47S CCND1 mutations increased CCND1 protein levels in MCL cell lines. Mechanistically, these mutations stabilized CCND1 protein through attenuation of threonine-286 phosphorylation, which is important for proteolysis through the ubiquitin-proteasome pathway...
October 4, 2016: Oncotarget
Christine Lefebvre, Evelyne Callet-Bauchu, Elise Chapiro, Nathalie Nadal, Dominique Penther, Hélène Antoine-Poirel
Non-Hodgkin's lymphomas and lymphoproliferative disorders include a high number of heterogeneous entities, described in the 2008 WHO classification. This classification reflects the crucial role of a multidisciplinary approach which integrates cytogenetic results both for the notion of clonality and for differential diagnosis between these entities. The prognostic impact of some cytogenetic abnormalities or genome complexity is also confirmed for many of these entities. Novel provisional entities have been described, such as BCLU (B-cell lymphoma unclassifiable with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma) for which karyotype is critical to distinguish BCLU from Burkitt's lymphoma...
October 1, 2016: Annales de Biologie Clinique
Melanie R Hassler, Walter Pulverer, Ranjani Lakshminarasimhan, Elisa Redl, Julia Hacker, Gavin D Garland, Olaf Merkel, Ana-Iris Schiefer, Ingrid Simonitsch-Klupp, Lukas Kenner, Daniel J Weisenberger, Andreas Weinhaeusel, Suzanne D Turner, Gerda Egger
Aberrant DNA methylation patterns in malignant cells allow insight into tumor evolution and development and can be used for disease classification. Here, we describe the genome-wide DNA methylation signatures of NPM-ALK-positive (ALK+) and NPM-ALK-negative (ALK-) anaplastic large-cell lymphoma (ALCL). We find that ALK+ and ALK- ALCL share common DNA methylation changes for genes involved in T cell differentiation and immune response, including TCR and CTLA-4, without an ALK-specific impact on tumor DNA methylation in gene promoters...
October 4, 2016: Cell Reports
Therese Högfeldt, Crystal Jaing, Kevin Mc Loughlin, James Thissen, Shea Gardner, Abeer A Bahnassy, Baback Gharizadeh, Joachim Lundahl, Anders Österborg, Anna Porwit, Abdel-Rahman N Zekri, Hussein M Khaled, Håkan Mellstedt, Ali Moshfegh
Diffuse large B-cell lymphoma (DLBCL), the most common type of non-Hodgkin's lymphoma (NHL) in adults, accounts for approximately 30-40% of newly diagnosed lymphomas worldwide. Environmental factors, such as viruses and bacteria, may contribute to cancer development through chronic inflammation and the integration of oncogenes, and have previously been indicated in cervical cancer, hepatocellular carcinoma, gastric cancer and lymphoproliferative disorders. In the present study, the presence of microbial agents was analyzed in the lymphoma tissue of patients with activated B-cell like (ABC) DLBCL...
October 2016: Oncology Letters
Elena M Cortizas, Astrid Zahn, Shiva Safavi, Joseph A Reed, Francisco Vega, Javier M Di Noia, Ramiro E Verdun
Activation-induced deaminase (AID) initiates antibody gene diversification by creating G:U mismatches in the immunoglobulin loci. However, AID also deaminates nonimmunoglobulin genes, and failure to faithfully repair these off-target lesions can cause B cell lymphoma. In this study, we identify a mechanism by which processing of G:U produced by AID at the telomeres can eliminate B cells at risk of genomic instability. We show that telomeres are off-target substrates of AID and that B cell proliferation depends on protective repair by uracil-DNA glycosylase (UNG)...
October 3, 2016: Journal of Experimental Medicine
Carlo M Croce, John C Reed
Resistance to cell death represents one of the hallmarks of cancer. Various genetic and epigenetic changes in malignant cells afford cytoprotection in the face of genomic instability, oncogene activation, microenvironment stress, chemotherapy, targeted anticancer drugs, and even immunotherapy. Central among the regulators of cell life and death are Bcl-2 family proteins, with the founding member of the family (B-cell lymphoma/leukemia-2) discovered via its involvement in chromosomal translocations in lymphomas...
October 15, 2016: Cancer Research
Staci L Haney, G Michael Upchurch, Jana Opavska, David Klinkebiel, Ryan A Hlady, Sohini Roy, Samikshan Dutta, Kaustubh Datta, Rene Opavsky
DNA methyltransferase 3A (DNMT3A) is an enzyme involved in DNA methylation that is frequently mutated in human hematologic malignancies. We have previously shown that inactivation of Dnmt3a in hematopoietic cells results in chronic lymphocytic leukemia in mice. Here we show that 12% of Dnmt3a-deficient mice develop CD8+ mature peripheral T cell lymphomas (PTCL) and 29% of mice are affected by both diseases. 10% of Dnmt3a+/- mice develop lymphomas, suggesting that Dnmt3a is a haploinsufficient tumor suppressor in PTCL...
September 2016: PLoS Genetics
Marco Herling, Benjamin Rengstl, René Scholtysik, Sylvia Hartmann, Ralf Küppers, Martin-Leo Hansmann, Hans H Diebner, Ingo Roeder, Hinrich Abken, Sebastian Newrzela, Jörg Kirberg
Growing attention in mature T-cell lymphomas/leukemias (MTCL) is committed to more accurate and meaningful classifications, improved pathogenetic concepts and expanded therapeutic options. This requires considerations of the immunologic concepts of T-cell homeostasis and the specifics of T-cell receptor (TCR) affinities and signaling. Scientists from various disciplines established the CONTROL-T research unit and in an international conference on MTCL they brought together experts from T-cell immunity, oncology, immunotherapy and systems biology...
September 19, 2016: Leukemia & Lymphoma
Sarah C Roode, Daniel Rotroff, Kristy L Richards, Peter Moore, Alison Motsinger-Reif, Yasuhiko Okamura, Takuya Mizuno, Hajime Tsujimoto, Steven E Suter, Matthew Breen
BACKGROUND: Leukemia/lymphoma cell lines have been critical in the investigation of the pathogenesis and therapy of hematological malignancies. While human LL cell lines have generally been found to recapitulate the primary tumors from which they were derived, appropriate characterization including cytogenetic and transcriptional assessment is crucial for assessing their clinical predictive value. RESULTS: In the following study, five canine LL cell lines, CLBL-1, Ema, TL-1 (Nody-1), UL-1, and 3132, were characterized using extensive immunophenotyping, karyotypic analysis, oligonucleotide array comparative genomic hybridization (oaCGH), and gene expression profiling...
2016: BMC Veterinary Research
Luca Aresu
Diffuse large B-cell lymphoma (DLBCL) is the most common canine aggressive B-cell lymphoma worldwide, and new recent molecular approaches have shown that DLBCL constitutes a heterogeneous tumor that cannot be unraveled by morphology and immunophenotype. DLBCL behaves aggressively, typically progressing over a short period of time, and the therapy response may be difficult to be predicted. Recently, the rate of bone marrow infiltration by flow cytometry has been demonstrated to be prognostic, but more sensible markers are needed...
2016: Frontiers in Veterinary Science
Helen Auburn, Mark Zuckerman, Melvyn Smith
AbstractIn order to develop novel host/pathogen real- time PCR assays for routine diagnostic use, early gene expression patterns from both Epstein-Barr virus (EBV) and Raji cells were examined after inducing the lytic life cycle using 12-O-tetradecanoyl-13-phorbol ester (TPA) and sodium butyrate. Real-time PCR identified several highly induced (>90-fold) EBV lytic genes over a 48 hr time-course during the lytic induction phase. Latent genes were induced at low levels during this phase. The cellular response to lytic viral replication is poorly understood...
September 12, 2016: Journal of Medical Microbiology
Walid Sabri Hamadou, Sawsen Besbes, Violaine Bourdon, Yosra Ben Youssef, Mohamed Adnène Laatiri, Testsuro Noguchi, Abderrahim Khélif, Hagay Sobol, Zohra Soua
Mutations are responsible for familial cancer syndromes which account for approximately 5-10 % of all types of cancers. Familial cancers are often caused by genetic alterations occurring either in tumor suppressor or genomic stability genes such as TP53. In this study, we have analyzed the TP53 gene by direct sequencing approach, in a panel of 18 Tunisian familial hematological malignancies cases including several forms of leukemia, lymphoma and myeloid syndrome and 22 cases of sporadic acute leukemia. In one familial case diagnosed with acute lymphoblastic leukemia, we reported an intronic substitution 559+1 G>A which may disrupt the splice site and impact the normal protein function...
September 12, 2016: Familial Cancer
Qinghua Cao, Fang Liu, Shurong Li, Ni Liu, Lihui Li, Changzhao Li, Tingsheng Peng
BACKGROUND: Primary anaplastic large cell lymphoma, ALK positive in small intestine is clinically rare and the clinical, radiological and pathological information are generally not available. Here, we report a case of 32-year-old male with ALK positive anaplastic large cell lymphoma at the junction of jejunum and ileum, and highlight the clinicopathological features and the differential diagnosis of this type lymphoma. CASE PRESENTATION: The patient presented with right middle abdominal mass for 1 month with sporadic pain...
2016: Diagnostic Pathology
Shiho Hoshina, Tsuyoshi Sekizuka, Michiyo Kataoka, Hideki Hasegawa, Hiromichi Hamada, Makoto Kuroda, Harutaka Katano
Exosomes are small vesicles released from cells, into which microRNAs (miRNA) are specifically sorted and accumulated. Two gamma-herpesviruses, Kaposi sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV), encode miRNAs in their genomes and express virus-encoded miRNAs in cells and exosomes. However, there is little information about the detailed distribution of virus-encoded miRNAs in cells and exosomes. In this study, we thus identified virus- and host-encoded miRNAs in exosomes released from KSHV- or EBV-infected lymphoma cell lines and compared them with intracellular miRNAs using a next-generation sequencer...
2016: PloS One
Ferdinandos Skoulidis, Vassiliki A Papadimitrakopoulou
Over the last 2 years, our therapeutic armamentarium against genomically defined subgroups of non-small cell lung cancer (NSCLC) has extended to patients with acquired resistance to front-line targeted therapy. Alectinib (Alecensa; Roche/Genentech), a second-generation, orally active, potent, and highly selective inhibitor of anaplastic lymphoma kinase (ALK), is indicated for patients with metastatic, ALK rearrangement-positive NSCLC whose disease has worsened after treatment with crizotinib or who became intolerant to the drug...
September 8, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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