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https://www.readbyqxmd.com/read/28337768/tet2-mutations-in-b-cells-of-patients-affected-by-angioimmunoblastic-t-cell-lymphoma
#1
Friederike H Schwartz, Qian Cai, Eva Fellmann, Sylvia Hartmann, Mikko I Mäyränpää, Marja-Liisa Karjalainen-Lindsberg, Christer Sundström, René Scholtysik, Martin-Leo Hansmann, Ralf Küppers
Angioimmunoblastic T cell lymphomas (AITL) frequently carry mutations in the TET2 and IDH2 genes. TET2 mutations represent early genetic lesions as they were already detected in hematopoietic precursor cells of AITL patients. We show by analysis of whole tissue sections and microdissected PD1(+) cells that the frequency of TET2-mutated AITL is presumably even higher than reported (12/13 cases in our collection, 92%). In two thirds of informative AITL (6/9) also a fraction of B cells was TET2-mutated. Investigation of four AITL by TET2 and IGHV gene sequencing of single microdissected B cells showed that between 10-60% of polyclonal B cells in AITL lymph nodes harboured the identical TET2 mutations of the respective T cell lymphoma clone...
March 24, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28335496/quantitative-analysis-of-the-kshv-transcriptome-following-primary-infection-of-blood-and-lymphatic-endothelial-cells
#2
A Gregory Bruce, Serge Barcy, Terri DiMaio, Emilia Gan, H Jacques Garrigues, Michael Lagunoff, Timothy M Rose
The transcriptome of the Kaposi's sarcoma-associated herpesvirus (KSHV/HHV8) after primary latent infection of human blood (BEC), lymphatic (LEC) and immortalized (TIME) endothelial cells was analyzed using RNAseq, and compared to long-term latency in BCBL-1 lymphoma cells. Naturally expressed transcripts were obtained without artificial induction, and a comprehensive annotation of the KSHV genome was determined. A set of unique coding sequence (UCDS) features and a process to resolve overlapping transcripts were developed to accurately quantitate transcript levels from specific promoters...
March 19, 2017: Pathogens
https://www.readbyqxmd.com/read/28329770/antigen-presentation-profiling-reveals-recognition-of-lymphoma-immunoglobulin-neoantigens
#3
Michael S Khodadoust, Niclas Olsson, Lisa E Wagar, Ole A W Haabeth, Binbin Chen, Kavya Swaminathan, Keith Rawson, Chih Long Liu, David Steiner, Peder Lund, Samhita Rao, Lichao Zhang, Caleb Marceau, Henning Stehr, Aaron M Newman, Debra K Czerwinski, Victoria E H Carlton, Martin Moorhead, Malek Faham, Holbrook E Kohrt, Jan Carette, Michael R Green, Mark M Davis, Ronald Levy, Joshua E Elias, Ash A Alizadeh
Cancer somatic mutations can generate neoantigens that distinguish malignant from normal cells. However, the personalized identification and validation of neoantigens remains a major challenge. Here we discover neoantigens in human mantle-cell lymphomas by using an integrated genomic and proteomic strategy that interrogates tumour antigen peptides presented by major histocompatibility complex (MHC) class I and class II molecules. We applied this approach to systematically characterize MHC ligands from 17 patients...
March 22, 2017: Nature
https://www.readbyqxmd.com/read/28328987/a-novel-recombinant-variant-of-latent-membrane-protein-1-from-epstein-barr-virus-in-argentina-denotes-phylogeographical-association
#4
Magdalena Gantuz, Mario Alejandro Lorenzetti, Paola Andrea Chabay, María Victoria Preciado
AIM: To study LMP1 variants distribution among children with EBV+ malignant and benign conditions as well as in healthy carriers. METHODS: Oral secretions and blood cells from 31 children with IM, and biopsies from 14 EBV+ reactive lymphoid hyperplasia and 33 EBV+ lymphomas were included. LMP1 was amplified by nested PCR and sequenced. Phylogenetic reconstructions were made under Maximun Likelihood, Bayesian and coalescent algorithms. RESULTS: Six clades were defined (China1, China2, Med-, Alaskan, B95...
2017: PloS One
https://www.readbyqxmd.com/read/28328317/antiproliferative-and-apoptotic-effects-of-novel-anti-ror1-single-chain-antibodies-in-hematological-malignancies
#5
Leili Aghebati-Maleki, Vahid Younesi, Behzad Baradaran, Jalal Abdolalizadeh, Morteza Motallebnezhad, Hamid Nickho, Dariush Shanehbandi, Jafar Majidi, Mehdi Yousefi
Receptor tyrosine kinase-like orphan receptor (ROR) proteins are a conserved family of tyrosine kinase receptors that function in developmental processes including cell survival, differentiation, cell migration, cell communication, cell polarity, proliferation, metabolism, and angiogenesis. ROR1 has recently been shown to be expressed in various types of cancer cells but not normal cells. Pharmacokinetics and pharmacodynamics of single-chain Fragment variable (scFv) antibodies provide potential therapeutic advantages over whole antibody molecules...
April 2017: SLAS Discov
https://www.readbyqxmd.com/read/28327945/enhancing-knowledge-discovery-from-cancer-genomics-data-with-galaxy
#6
Marco A Albuquerque, Bruno M Grande, Elie J Ritch, Prasath Pararajalingam, Selin Jessa, Martin Krzywinski, Jasleen K Grewal, Sohrab P Shah, Paul C Boutros, Ryan D Morin
The field of cancer genomics has demonstrated the power of massively parallel sequencing techniques to inform on the genes and specific alterations that drive tumor onset and progression. Although large comprehensive sequence data sets continue to be made increasingly available, data analysis remains an ongoing challenge, particularly for laboratories lacking dedicated resources and bioinformatics expertise. To address this, we have produced a collection of Galaxy tools that represent many popular algorithms for detecting somatic genetic alterations from cancer genome and exome data...
March 9, 2017: GigaScience
https://www.readbyqxmd.com/read/28303495/genetic-landscape-and-classification-of-peripheral-t-cell-lymphomas
#7
REVIEW
Rosalind F Sandell, Rebecca L Boddicker, Andrew L Feldman
PURPOSE OF REVIEW: Peripheral T cell lymphomas (PTCLs) are markedly heterogeneous at the clinical, pathological, and molecular levels. This review will discuss genetic findings in PTCL with special emphasis on how they impact lymphoma classification. RECENT FINDINGS: Sequencing studies have identified recurrent genetic alterations in nearly every PTCL subtype. In anaplastic large cell lymphoma, these studies have revealed novel chromosomal rearrangements and mutations that have prognostic significance and may suggest new therapeutic approaches...
April 2017: Current Oncology Reports
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
#8
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/28298040/noninvasive-assessment-of-isocitrate-dehydrogenase-mutation-status-in-cerebral-gliomas-by-magnetic-resonance-spectroscopy-in-a-clinical-setting
#9
Anna Tietze, Changho Choi, Bruce Mickey, Elizabeth A Maher, Benedicte Parm Ulhøi, Ryan Sangill, Yasmin Lassen-Ramshad, Slavka Lukacova, Leif Østergaard, Gorm von Oettingen
OBJECTIVE Mutations in the isocitrate dehydrogenase (IDH) genes are of proven diagnostic and prognostic significance for cerebral gliomas. The objective of this study was to evaluate the clinical feasibility of using a recently described method for determining IDH mutation status by using magnetic resonance spectroscopy (MRS) to detect the presence of 2-hydroxyglutarate (2HG), the metabolic product of the mutant IDH enzyme. METHODS By extending imaging time by 6 minutes, the authors were able to include a point-resolved spectroscopy (PRESS) MRS sequence in their routine glioma imaging protocol...
March 3, 2017: Journal of Neurosurgery
https://www.readbyqxmd.com/read/28297626/clinical-applications-of-the-genomic-landscape-of-aggressive-non-hodgkin-lymphoma
#10
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/28297623/clinical-implications-of-novel-genomic-discoveries-in-chronic-lymphocytic-leukemia
#11
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/28293795/a-workflow-for-in-silico-design-of-hil-10-and-ebvil-10-inhibitors-using-well-known-miniprotein-scaffolds
#12
Salvador Dueñas, Sergio A Aguila, Genaro Pimienta
The over-expression of immune-suppressors such as IL-10 is a crucial landmark in both tumor progression, and latent viral and parasite infection. IL-10 is a multifunctional protein. Besides its immune-cell suppressive function, it also promotes B-cell tumorigenesis of lymphomas and melanoma. Human pathogens like unicellular parasites and viruses that remain latent inside B cells promote the over-expression of hIL-10 upon infection, which inhibits cell-mediated immune surveillance, and at the same time mediates B cell proliferation...
April 2017: Journal of Molecular Modeling
https://www.readbyqxmd.com/read/28284718/novel-jak3-activating-mutations-in-extranodal-nk-t-cell-lymphoma-nasal-type
#13
Sung H Sim, Soyeon Kim, Tae M Kim, Yoon K Jeon, Soo J Nam, Yong-Oon Ahn, Bhumsuk Keam, Hyun H Park, Dong-Wan Kim, Chul W Kim, Dae S Heo
Inhibition of the Janus kinase (JAK)-STAT pathway has been implicated as a treatment option for extranodal natural killer/T-cell lymphoma, nasal type (NTCL). However, JAK-STAT pathway alterations in NTCL are variable, and the efficacy of JAK-STAT pathway inhibition has been poorly evaluated. JAK3 mutation and STAT3 genetic alterations were investigated by direct sequencing and immunohistochemistry in 84 patients with newly diagnosed NTCL. Five of 71 patients with NTCL (7.0%) had JAK3 mutations in the pseudokinase domain: two JAK3(A573V), two JAK3(H583Y), and one JAK3(G589D) mutation...
March 8, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28284183/multiparametric-cardiac-magnetic-resonance-imaging-cmr-for-the-diagnosis-of-loeffler-s-endocarditis-a-case-report
#14
Mareike Gastl, Patrick Behm, Christoph Jacoby, Malte Kelm, Florian Bönner
BACKGROUND: Endocarditis parietalis fibroplastica Löfflein (EPF) is a rare form of primary restrictive cardiomyopathy with poor prognosis. It is generally caused by hypereosinophilic syndrome with eosinophilic penetration of the heart. This leads to congestive heart failure in three different stages. As a frequent manifestation of neoplastic diseases, cardiac involvement means poor prognosis. CASE PRESENTATION: The present report deals with a case of EPF caused by non-specified T-cell lymphoma (T-NOS)...
March 11, 2017: BMC Cardiovascular Disorders
https://www.readbyqxmd.com/read/28280994/detection-of-myd88-l265p-and-whim-like-cxcr4-mutation-in-patients-with-igm-monoclonal-gammopathy-related-disease
#15
Xin-Xin Cao, Qi Meng, Hao Cai, Tian-Hua He, Cong-Li Zhang, Wei Su, Jian Sun, Yue Li, Wei Xu, Dao-Bin Zhou, Jian Li
A broad spectrum of diseases are associated with IgM monoclonal gammopathy, including Waldenstrom macroglobulinemia (WM), various types of B cell non-Hodgkin's lymphoma (NHL), multiple myeloma (MM), primary amyloidosis (AL), and monoclonal gammopathy of undetermined significance (MGUS); these are called IgM monoclonal gammopathy related diseases (IgM-RD). We investigated MYD88 L265P and WHIM-like CXCR4 mutations in various IgM-RD. Patients with serum immunofixation electrophoresis confirmed IgM monoclonal gammopathy who had enough material for DNA extraction and presented between January 2008 and October 2016 at Peking Union Medical College Hospital were enrolled in this cohort...
March 9, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28280620/potential-actionable-targets-in-appendiceal-cancer-detected-by-immunohistochemistry-fluorescent-in-situ-hybridization-and-mutational-analysis
#16
Erkut Borazanci, Sherri Z Millis, Jeffery Kimbrough, Nancy Doll, Daniel Von Hoff, Ramesh K Ramanathan
BACKGROUND: Appendiceal cancers are rare and consist of carcinoid, mucocele, pseudomyxoma peritonei (PMP), goblet cell carcinoma, lymphoma, and adenocarcinoma histologies. Current treatment involves surgical resection or debulking, but no standard exists for adjuvant chemotherapy or treatment for metastatic disease. METHODS: Samples were identified from approximately 60,000 global tumors analyzed at a referral molecular profiling CLIA-certified laboratory. A total of 588 samples with appendix primary tumor sites were identified (male/female ratio of 2:3; mean age =55)...
February 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28278699/malt1-sequencing-analyses-in-marginal-zone-b-cell-lymphomas-reveal-mutations-in-the-translocated-malt1-allele-in-an-igh-malt1-positive-malt-lymphoma
#17
Nuray Akyüz, Nadine Albert-Konetzny, Christiane Pott, Evelyne Callet-Bauchu, Carsten Bokemeyer, Eva Maria Murga Penas, Judith Dierlamm
No abstract text is available yet for this article.
March 2, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28277671/enzyme-cleavable-polymeric-micelles-for-the-intracellular-de-livery-of-pro-apoptotic-peptides
#18
Hanna B Kern, Selvi Srinivasan, Anthony J Convertine, David Hockenbery, Oliver W Press, Patrick S Stayton
Peptides derived from the third Bcl-2 homology domain (BH3) renormalize apoptotic signaling by antagonizing pro-survival Bcl-2 family members. They serve as a model for potential peptide drugs that possess therapeutic activities but are limited by delivery barriers including short circulation half-lives and poor penetration into cells. A diblock polymeric micelle carrier for the BIM BH3 peptide was recently described that demonstrated anti-tumor activity in a B-cell lymphoma xenograft model [Berguig et al., Mol Ther, 2015]...
March 9, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28273192/-primary-central-nervous-system-lymphoma-pathogenesis-and-histomorphology
#19
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/28272989/phase-i-clinical-trial-of-idiotypic-dna-vaccine-administered-as-a-complex-with-polyethylenimine-to-patients-with-b-cell-lymphoma
#20
A N Meleshko, N A Petrovskaya, N Savelyeva, K P Vashkevich, S N Doronina, N V Sachivko
We report on the design of a phase I, non-randomized, open-label study of idiotypic DNA vaccination in patients with B-cell non-Hodgkin's lymphoma (ISRCTN31090206). The study uses DNA fusion gene vaccination encoding patient-specific single chain variable fragment, or idiotype, linked to an immunostimulatory sequence. Two types of immunostimulatory sequence are being explored: potato virus X coat protein and human chemokine MIP3α. Linear polyethylenimine with low molecular weight (8 kDa) is used as a synthetic vehicle for vaccine delivery...
March 8, 2017: Human Vaccines & Immunotherapeutics
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