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Genomic lymphoma

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https://www.readbyqxmd.com/read/28302137/mutations-of-crebbp-and-socs1-are-independent-prognostic-factors-in-diffuse-large-b-cell-lymphoma-mutational-analysis-of-the-sakk-38-07-prospective-clinical-trial-cohort
#1
Darius Juskevicius, David Jucker, Dirk Klingbiel, Christoph Mamot, Stephan Dirnhofer, Alexandar Tzankov
BACKGROUND/PURPOSE: Recently, the mutational background of diffuse large B cell lymphoma (DLBCL) has been revealed, identifying specific genetic events that drive lymphomagenesis. However, the prognostic value of these mutations remains to be determined. Prognostic biomarkers in DLBCL are urgently needed, since the current clinical parameter-based factors (e.g., International Prognostic Index (IPI)) are insufficient, particularly in identifying patients with poor prognosis who might benefit from alternative treatments...
March 17, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28298901/unveiling-another-missing-piece-in-ebv-driven-lymphomagenesis-ebv-encoded-micrornas-expression-in-eber-negative-burkitt-lymphoma-cases
#2
Lucia Mundo, Maria R Ambrosio, Matteo Picciolini, Giuseppe Lo Bello, Sara Gazaneo, Leonardo Del Porro, Stefano Lazzi, Mohsen Navari, Noel Onyango, Massimo Granai, Cristiana Bellan, Giulia De Falco, Davide Gibellini, Pier P Piccaluga, Lorenzo Leoncini
Epstein-Barr virus (EBV) is a gammaherpesvirus linked to a number of lymphoid and epithelial malignancies, including Burkitt lymphoma (BL) in which its frequency ranges from 30% in sporadic cases to 100% in the endemic ones. The possible contribution of EBV to BL pathogenesis is largely unknown. It has been suggested that EBV may be associated with all of the cases, including those diagnosed as EBV negative by a mechanism of hit-and-run. Early during oncogenesis, viral genes are essential for initiating disease...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28297626/clinical-applications-of-the-genomic-landscape-of-aggressive-non-hodgkin-lymphoma
#3
Andrea B Moffitt, Sandeep S Dave
In this review, we examine the genomic landscapes of lymphomas that arise from B, T, and natural killer cells. Lymphomas represent a striking spectrum of clinical behaviors. Although some lymphomas are curable with standard therapy, the majority of the affected patients succumb to their disease. Here, the genetic underpinnings of these heterogeneous entities are reviewed. We consider B-cell lymphomas, including Burkitt lymphoma, diffuse large B-cell lymphoma, Hodgkin lymphoma, and primary mediastinal B-cell lymphoma...
March 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28297625/genomics-of-hairy-cell-leukemia
#4
Enrico Tiacci, Valentina Pettirossi, Gianluca Schiavoni, Brunangelo Falini
Hairy cell leukemia (HCL) is a chronic mature B-cell neoplasm with unique clinicopathologic features and an initial exquisite sensitivity to chemotherapy with purine analogs; however, the disease relapses, often repeatedly. The enigmatic pathogenesis of HCL was recently clarified by the discovery of its underlying genetic cause, the BRAF-V600E kinase-activating mutation, which is somatically and clonally present in almost all patients through the entire disease spectrum and clinical course. By aberrantly activating the RAF-MEK-ERK signaling pathway, BRAF-V600E shapes key biologic features of HCL, including its specific expression signature, hairy morphology, and antiapoptotic behavior...
March 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28297623/clinical-implications-of-novel-genomic-discoveries-in-chronic-lymphocytic-leukemia
#5
Gregory Lazarian, Romain Guièze, Catherine J Wu
Chronic lymphocytic leukemia (CLL) is a common B-cell malignancy with a remarkably heterogeneous course, ranging from indolent disease with no need for immediate therapy to rapidly progressive disease associated with therapeutic resistance. The recent US Food and Drug Administration approvals of novel targeted therapies such as inhibitors of B-cell receptor signaling and B-cell lymphoma 2 have opened up new opportunities in the clinical management of patients with CLL and heralded a new era in the clinical treatment of this disease...
March 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28288716/molecular-pathogenesis-of-splenic-and-nodal-marginal-zone-lymphoma
#6
REVIEW
Valeria Spina, Davide Rossi
Genomic studies have improved our understanding of the biological basis of splenic (SMZL) and nodal (NMZL) marginal zone lymphoma by providing a comprehensive and unbiased view of the genes/pathways that are deregulated in these diseases. Consistent with the physiological involvement of NOTCH, NF-κB, B-cell receptor and toll-like receptor signaling in mature B-cells differentiation into the marginal zone B-cells, many oncogenic mutations of genes involved in these pathways have been identified in SMZL and NMZL...
March 2017: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/28288713/methylation-patterns-in-marginal-zone-lymphoma
#7
REVIEW
Alberto J Arribas, Francesco Bertoni
Promoter DNA methylation is a major regulator of gene expression and transcription. The identification of methylation changes is important for understanding disease pathogenesis, for identifying prognostic markers and can drive novel therapeutic approaches. In this review we summarize the current knowledge regarding DNA methylation in MALT lymphoma, splenic marginal zone lymphoma, nodal marginal zone lymphoma. Despite important differences in the study design for different publications and the existence of a sole large and genome-wide methylation study for splenic marginal zone lymphoma, it is clear that DNA methylation plays an important role in marginal zone lymphomas, in which it contributes to the inactivation of tumor suppressors but also to the expression of genes sustaining tumor cell survival and proliferation...
March 2017: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/28282431/interactions-within-the-mhc-contribute-to-the-genetic-architecture-of-celiac-disease
#8
Benjamin Goudey, Gad Abraham, Eder Kikianty, Qiao Wang, Dave Rawlinson, Fan Shi, Izhak Haviv, Linda Stern, Adam Kowalczyk, Michael Inouye
Interaction analysis of GWAS can detect signal that would be ignored by single variant analysis, yet few robust interactions in humans have been detected. Recent work has highlighted interactions in the MHC region between known HLA risk haplotypes for various autoimmune diseases. To better understand the genetic interactions underlying celiac disease (CD), we have conducted exhaustive genome-wide scans for pairwise interactions in five independent CD case-control studies, using a rapid model-free approach to examine over 500 billion SNP pairs in total...
2017: PloS One
https://www.readbyqxmd.com/read/28273192/-primary-central-nervous-system-lymphoma-pathogenesis-and-histomorphology
#9
Gábor Méhes
Lymphoproliferative diseases of the central nervous system are rare, diagnostics and treatment are accordingly challenging. Since the introduction of the 2008 WHO lymphoma classification, primary CNS DLBCL - also covering the associated primary ocular (vitreoretinal) lymphoma - is a separate entity. The special localization is related with a series of newly recognized genetic, genomic and immunologic features directing to the strong interaction between transformed lymphoma cells, neural tissue components and the local immune response...
March 8, 2017: Magyar Onkologia
https://www.readbyqxmd.com/read/28271981/understanding-epstein-barr-virus-life-cycle-with-proteomics-a-temporal-analysis-of-ubiquitination-during-virus-reactivation
#10
Dong-Wen Lv, Jun Zhong, Kun Zhang, Akhilesh Pandey, Renfeng Li
Epstein-Barr virus (EBV) is a human γ-herpesvirus associated with cancer, including Burkitt lymphoma, nasopharyngeal, and gastric carcinoma. EBV reactivation in latently infected B cells is essential for persistent infection whereby B cell receptor (BCR) activation is a physiologically relevant stimulus. Yet, a global view of BCR activation-regulated protein ubiquitination is lacking when EBV is actively replicating. We report here, for the first time, the long-term effects of IgG cross-linking-regulated protein ubiquitination and offer a basis for dissecting the cellular environment during the course of EBV lytic replication...
January 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28264017/ncoa1-is-a-novel-susceptibility-gene-for-multiple-myeloma-in-the-chinese-population-a-case-control-study
#11
Mengle Peng, Guanfei Zhao, Funing Yang, Guixue Cheng, Jing Huang, Xiaosong Qin, Yong Liu, Qingtao Wang, Yongzhe Li, Dongchun Qin
Multiple myeloma (MM) is an incurable malignancy of mature B-lymphoid cells, and its pathogenesis is only partially understood. Previous studies have demonstrated that a number of Non-Hodgkin Lymphoma (NHL) associated genes also show susceptibility to MM, suggesting malignancies originating from B cells may share similar genetic susceptibility. Several recent large-scale genome-wide association studies (GWAS) have identified HLA-I, HLA-II, CXCR5, ETS1, LPP and NCOA1 genes as genetic risk factors associated with NHL, and this study aimed to investigate whether these genes polymorphisms confer susceptibility with MM in the Chinese Han population...
2017: PloS One
https://www.readbyqxmd.com/read/28263674/human-t-cell-leukemia-virus-type-1-and-eye-diseases
#12
Yukiko Terada, Koju Kamoi, Takashi Komizo, Kazunori Miyata, Manabu Mochizuki
Human T cell leukemia virus type 1, also known as human T lymphotropic virus type 1 (HTLV-1), is a retrovirus that encodes a reverse transcriptase, which translates viral RNA into a DNA provirus that is integrated into the host genome. The virus was found to be a causative agent of adult T cell leukemia/lymphoma (ATL) in the early 1980s, and was also found to cause the neurological disorder tropical spastic paraparesis (TSP)/HTLV-1-associated myelopathy (HAM) and the inflammatory disorder HTLV-1 uveitis in the mid 1980s and early 1990s, respectively...
March 1, 2017: Journal of Ocular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28262675/genomic-characterisation-of-e%C3%AE-myc-mouse-lymphomas-identifies-bcor-as-a-myc-co-operative-tumour-suppressor-gene
#13
Marcus Lefebure, Richard W Tothill, Elizabeth Kruse, Edwin D Hawkins, Jake Shortt, Geoffrey M Matthews, Gareth P Gregory, Benjamin P Martin, Madison J Kelly, Izabela Todorovski, Maria A Doyle, Richard Lupat, Jason Li, Jan Schroeder, Meaghan Wall, Stuart Craig, Gretchen Poortinga, Don Cameron, Megan Bywater, Lev Kats, Micah D Gearhart, Vivian J Bardwell, Ross A Dickins, Ross D Hannan, Anthony T Papenfuss, Ricky W Johnstone
The Eμ-Myc mouse is an extensively used model of MYC driven malignancy; however to date there has only been partial characterization of MYC co-operative mutations leading to spontaneous lymphomagenesis. Here we sequence spontaneously arising Eμ-Myc lymphomas to define transgene architecture, somatic mutations, and structural alterations. We identify frequent disruptive mutations in the PRC1-like component and BCL6-corepressor gene Bcor. Moreover, we find unexpected concomitant multigenic lesions involving Cdkn2a loss and other cancer genes including Nras, Kras and Bcor...
March 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/28260016/effects-of-r-type-and-s-type-ginsenoside-rg3-on-dna-methylation-in-human-hepatocarcinoma-cells
#14
Siying Teng, Yi Wang, Pingya Li, Jinhua Liu, Anhui Wei, Haotian Wang, Xiangkun Meng, Di Pan, Xinmin Zhang
Ginsenoside Rg3, a bioactive constituent isolated from Panax ginseng, exhibits antitumorigenic, antioxidative, antiangiogenic, neuroprotective and other biological activities are associated with the regulation of multiple genes. DNA methylation patterns, particularly those in the promoter region, affect gene expression, and DNA methylation is catalyzed by DNA methylases. However, whether ginsenoside Rg3 affects DNA methylation is unknown. High performance liquid chromatography assay, MspI/HpaII polymerase chain reaction (PCR) and reverse transcription‑quantitative PCR were performed to assess DNA methylation...
February 28, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28249162/bet-bromodomain-inhibitors-engage-the-host-immune-system-and-regulate-expression-of-the-immune-checkpoint-ligand-pd-l1
#15
Simon J Hogg, Stephin J Vervoort, Sumit Deswal, Christopher J Ott, Jason Li, Leonie A Cluse, Paul A Beavis, Phillip K Darcy, Benjamin P Martin, Andrew Spencer, Anna K Traunbauer, Irina Sadovnik, Karin Bauer, Peter Valent, James E Bradner, Johannes Zuber, Jake Shortt, Ricky W Johnstone
BET inhibitors (BETi) target bromodomain-containing proteins and are currently being evaluated as anti-cancer agents. We find that maximal therapeutic effects of BETi in a Myc-driven B cell lymphoma model required an intact host immune system. Genome-wide analysis of the BETi-induced transcriptional response identified the immune checkpoint ligand Cd274 (Pd-l1) as a Myc-independent, BETi target-gene. BETi directly repressed constitutively expressed and interferon-gamma (IFN-γ) induced CD274 expression across different human and mouse tumor cell lines and primary patient samples...
February 28, 2017: Cell Reports
https://www.readbyqxmd.com/read/28244148/detection-of-inherited-chromosomally-integrated-hhv-6-cihhv-6-in-a-marker-chromosome
#16
Diana Campioni, Valentina Gentili, Francesco Cavazzini, Daria Bortolotti, Elisabeth P Nacheva, Antonio Cuneo, Dario Di Luca, Roberta Rizzo
OBJECTIVES: Inherited chromosomally integrated human herpesvirus 6 (ciHHV-6) is characterized by the complete HHV-6 genome integration into the host germ line genome and is vertically transmitted with a Mendelian inheritance. By now, the only relationship between ciHHV-6 and diseases seems to be with angina pectoris. METHODS: We report a case of an 82 years old male diagnosed with Diffuse Large B-cell Lymphoma (DLBCL) on October 2014. To substantiate the suspicion of ciHHV-6, we analysed peripheral blood mononuclear cells, bone marrow biopsy and pleural effusion derived mesothelial cells with PCR, RT-PCR and FISH...
February 28, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28214593/jak-stat-pathway-directed-therapy-of-t-cell-leukemia-lymphoma-inspired-by-functional-and-structural-genomics
#17
REVIEW
Thomas A Waldmann
Abnormal activation of the γc cytokine JAK/STAT signaling pathway assessed by STAT3 or STAT5b phosphorylation was present in a proportion of many T-cell malignancies. Activating mutations of STAT3/STAT5b and JAK1/3 were present in some but not in all cases with constitutive signaling pathway activation. Using shRNA analysis pSTAT malignant T-cell lines were addicted to JAKs/STATs whether they were mutated or not. Activating JAK/STAT mutations were not sufficient to support leukemic cell proliferation but only augmented upstream pathway signals...
February 15, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28212290/defining-clinical-response-criteria-and-early-response-criteria-for-precision-oncology-current-state-of-the-art-and-future-perspectives
#18
Vivek Subbiah, Hubert H Chuang, Dhiraj Gambhire, Kalevi Kairemo
In this era of precision oncology, there has been an exponential growth in the armamentarium of genomically targeted therapies and immunotherapies. Evaluating early responses to precision therapy is essential for "go" versus "no go" decisions for these molecularly targeted drugs and agents that arm the immune system. Many different response assessment criteria exist for use in solid tumors and lymphomas. We reviewed the literature using the Medline/PubMed database for keywords "response assessment" and various known response assessment criteria published up to 2016...
February 15, 2017: Diagnostics
https://www.readbyqxmd.com/read/28211887/germline-mutations-predisposing-to-diffuse-large-b-cell-lymphoma
#19
REVIEW
O C Leeksma, N F de Miranda, H Veelken
Genetic studies of diffuse large B-cell lymphomas (DLBCLs) in humans have revealed numerous targets of somatic mutations and an increasing number of potentially relevant germline alterations. The latter often affect genes involved in DNA repair and/or immune function. In general, defects in these genes also predispose to other conditions. Knowledge of these mutations can lead to disease-preventing measures in the patient and relatives thereof. Conceivably, these germline mutations will be taken into account in future therapy of the lymphoma...
February 17, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28203297/therapeutic-approach-to-treating-patients-with-braf-mutant-lung-cancer-latest-evidence-and-clinical-implications
#20
REVIEW
Adrianus J de Langen, Egbert F Smit
Lung adenocarcinoma is known for its high rate of somatic mutations and genomic rearrangements. The identification of epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements that sensitize tumors to specific drugs has changed the therapeutic approach and prognosis in these molecularly-defined subgroups. Several other key genetic alterations have been identified, of which BRAF mutations are found in 4% of non-small cell lung cancer (NSCLC) cases. Targeted drugs against BRAF and downstream MEK were recently approved for the treatment of BRAF-positive melanoma and have entered clinical evaluation in NSCLC...
January 2017: Therapeutic Advances in Medical Oncology
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