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https://www.readbyqxmd.com/read/28436299/mgmt-gene-variants-temozolomide-myelotoxicity-and-glioma-risk-a-concise-literature-survey-including-an-illustrative-case
#1
Meric A Altinoz, Ilhan Elmaci, Fatih Han Bolukbasi, Cumhur Gokhan Ekmekci, Guven Yenmis, Ramazan Sari, Aydin Sav
Temozolomide may cause thrombocytopenia or neutropenia in 3-4% of glioblastoma patients, respectively. However, pancytopenia is rarely reported. MGMT (O6-methylguanine-DNA-methyltransferase) enzyme repairs temozolomide-induced DNA mutations and associates both with antitumour efficacy and myelosuppression. Many studies on the effects of MGMT gene-methylation on temozolomide's effects exist, but much fewer publications concerning MGMT variants were documented. A full sequencing of the MGMT gene was performed in a female glioblastoma patient, who developed pancytopenia following temozolomide treatment...
April 23, 2017: Journal of Chemotherapy
https://www.readbyqxmd.com/read/28432871/mir-24-3p-is-overexpressed-in-hodgkin-lymphoma-and-protects-hodgkin-and-reed-sternberg-cells-from-apoptosis
#2
Ye Yuan, Joost Kluiver, Jasper Koerts, Debora de Jong, Bea Rutgers, Fazlyn Reeny Abdul Razak, Martijn Terpstra, Boudewijn Plaat, Ilja M Nolte, Arjan Diepstra, Lydia Visser, Klaas Kok, Anke van den Berg
miRNAs play important roles in biological processes, such as proliferation, metabolism, differentiation, and apoptosis, whereas altered expression levels contribute to diseases, such as cancers. We identified miRNAs with aberrant expression in Hodgkin lymphoma (HL) and investigated their role in pathogenesis. Small RNA sequencing revealed 84 significantly differentially expressed miRNAs in HL cell lines as compared to germinal center B cells. Three up-regulated miRNAs-miR-23a-3p, miR-24-3p, and miR-27a-3p-were derived from one primary miRNA transcript...
April 19, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28430172/ezh2-alterations-in-follicular-lymphoma-biological-and-clinical-correlations
#3
S Huet, L Xerri, B Tesson, S Mareschal, S Taix, L Mescam-Mancini, E Sohier, M Carrère, J Lazarovici, O Casasnovas, L Tonon, S Boyault, S Hayette, C Haioun, B Fabiani, A Viari, F Jardin, G Salles
The histone methyltransferase EZH2 has an essential role in the development of follicular lymphoma (FL). Recurrent gain-of-function mutations in EZH2 have been described in 25% of FL patients and induce aberrant methylation of histone H3 lysine 27 (H3K27). We evaluated the role of EZH2 genomic gains in FL biology. Using RNA sequencing, Sanger sequencing and SNP-arrays, the mutation status, copy-number and gene-expression profiles of EZH2 were assessed in a cohort of 159 FL patients from the PRIMA trial. Immunohistochemical (IHC) EZH2 expression (n=55) and H3K27 methylation (n=63) profiles were also evaluated...
April 21, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28427013/the-accelerated-path-of-ceritinib-translating-pre-clinical-development-into-clinical-efficacy
#4
REVIEW
Tony S K Mok, Lucio Crino, Enriqueta Felip, Ravi Salgia, Tommaso De Pas, Daniel S W Tan, Laura Q M Chow
The discovery of anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC) in 2007 led to the development and subsequent approval of the ALK inhibitor crizotinib in 2011. However, despite its clinical efficacy, resistance to crizotinib invariably develops. There is now a next generation of ALK inhibitors, including two that have been approved-ceritinib and alectinib-and others that are in development-brigatinib, lorlatinib and X-396. Ceritinib and the other next-generation ALK inhibitors are more potent than crizotinib and can overcome tumor cell resistance mechanisms...
March 30, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28424246/enteropathy-associated-t-cell-lymphoma-subtypes-are-characterized-by-loss-of-function-of-setd2
#5
Andrea B Moffitt, Sarah L Ondrejka, Matthew McKinney, Rachel E Rempel, John R Goodlad, Chun Huat Teh, Sirpa Leppa, Susanna Mannisto, Panu E Kovanen, Eric Tse, Rex K H Au-Yeung, Yok-Lam Kwong, Gopesh Srivastava, Javeed Iqbal, Jiayu Yu, Kikkeri Naresh, Diego Villa, Randy D Gascoyne, Jonathan Said, Magdalena B Czader, Amy Chadburn, Kristy L Richards, Deepthi Rajagopalan, Nicholas S Davis, Eileen C Smith, Brooke C Palus, Tiffany J Tzeng, Jane A Healy, Patricia L Lugar, Jyotishka Datta, Cassandra Love, Shawn Levy, David B Dunson, Yuan Zhuang, Eric D Hsi, Sandeep S Dave
Enteropathy-associated T cell lymphoma (EATL) is a lethal, and the most common, neoplastic complication of celiac disease. Here, we defined the genetic landscape of EATL through whole-exome sequencing of 69 EATL tumors. SETD2 was the most frequently silenced gene in EATL (32% of cases). The JAK-STAT pathway was the most frequently mutated pathway, with frequent mutations in STAT5B as well as JAK1, JAK3, STAT3, and SOCS1 We also identified mutations in KRAS, TP53, and TERT Type I EATL and type II EATL (monomorphic epitheliotropic intestinal T cell lymphoma) had highly overlapping genetic alterations indicating shared mechanisms underlying their pathogenesis...
April 19, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28422997/promoter-hypermethylation-as-a-mechanism-for-lamin-a-c-silencing-in-a-subset-of-neuroblastoma-cells
#6
Ines Rauschert, Fabian Aldunate, Jens Preussner, Miguel Arocena-Sutz, Vanina Peraza, Mario Looso, Juan C Benech, Ruben Agrelo
Nuclear lamins support the nuclear envelope and provide anchorage sites for chromatin. They are involved in DNA synthesis, transcription, and replication. It has previously been reported that the lack of Lamin A/C expression in lymphoma and leukaemia is due to CpG island promoter hypermethylation. Here, we provide evidence that Lamin A/C is silenced via this mechanism in a subset of neuroblastoma cells. Moreover, Lamin A/C expression can be restored with a demethylating agent. Importantly, Lamin A/C reintroduction reduced cell growth kinetics and impaired migration, invasion, and anchorage-independent cell growth...
2017: PloS One
https://www.readbyqxmd.com/read/28421278/an-efficient-method-to-enrich-for-knock-out-and-knock-in-cellular-clones-using-the-crispr-cas9-system
#7
Francesca Niccheri, Riccardo Pecori, Silvestro G Conticello
Clustered Regularly Interspaced Short Palindromic Repeats-associated protein 9 nuclease (CRISPR/Cas9) and Transcription Activator-Like Effector Nucleases (TALENs) are versatile tools for genome editing. Here we report a method to increase the frequency of Cas9-targeted cellular clones. Our method is based on a chimeric construct with a Blasticidin S Resistance gene (bsr) placed out-of-frame by a surrogate target sequence. End joining of the CRISPR/Cas9-induced double-strand break on the surrogate target can place the bsr in frame, thus providing temporary resistance to Blasticidin S: this is used to enrich for cells where Cas9 is active...
April 18, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28419429/mutational-landscape-of-b-cell-post-transplant-lymphoproliferative-disorders
#8
Thomas Menter, Darius Juskevicius, Mary Alikian, Juerg Steiger, Stephan Dirnhofer, Alexandar Tzankov, Kikkeri N Naresh
It is currently unclear whether post-transplant diffuse large B-cell lymphomas (PT-DLBCL) display a similar genomic landscape as DLBCL in immunocompetent patients (IC-DLBCL). We investigated 50 post-transplant lymphoproliferative disorders (PTLDs) including 37 PT-DLBCL samples for somatic mutations frequently observed in IC-DLBCL. Targeted Next Generation Sequencing (NGS) using the Ion Torrent platform and a customized panel of 68 genes was performed on genomic DNA. Non-tumoural tissue was sequenced to exclude germline variants in cases where available...
April 17, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28419186/cd4-negative-variant-of-cutaneous-blastic-plasmacytoid-dendritic-cell-neoplasm-with-a-novel-pbrm1-mutation-in-an-11-year-old-girl
#9
Nuri Yigit, Luisa Fernanda Suarez, Lisa Giulino Roth, Attilio Orazi, Wayne Tam
Objectives: We report a rare case of CD4- cutaneous blastic plasmacytoid dendritic cell neoplasm (BPDCN) with a novel PBRM1 mutation. Methods: An 11-year-old girl presented with an enlarged mass on her left arm and underwent an incisional biopsy. Results: Histopathologic examination and immunohistochemistry studies showed a monotonous proliferation of blasts that were CD4-, CD56+, and CD123+. There was no evidence of leukemic dissemination...
April 15, 2017: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28415895/the-value-of-liquid-biopsy-in-diagnosis-and-monitoring-of-diffuse-large-b-cell-lymphoma-recent-developments-and-future-potential
#10
Vincent Camus, Fabrice Jardin, Herve Tilly
Diffuse large B-cell lymphomas (DLBCL) represent a heterogeneous subset of non-Hodgkin lymphomas (NHL) that demonstrate many molecular alterations and somatic mutations, all of which are targets for the recent development of biomarkers that use various molecular biological techniques. These non-invasive emerging biomarkers will be used in the next few years to better monitor the response to immunochemotherapeutic treatments with the aim of completely eradicating the disease in order to cure it. Areas covered: In this review, the authors conducted a literature search to identify and summarize the major advances in liquid biopsy techniques for DLBCL that are useful for diagnosis and monitoring minimal residual disease (MRD)...
April 18, 2017: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/28411252/prognostic-relevance-of-cd163-and-cd8-combined-with-ezh2-and-gain-of-chromosome-18-in-follicular-lymphoma-a-study-by-the-lunenburg-lymphoma-biomarker-consortium
#11
Wendy B C Stevens, Matias Mendeville, Robert Redd, Andrew J Clear, Reno Bladergroen, Maria Calaminici, Andreas Rosenwald, Eva Hoster, Wolfgang Hiddemann, Philippe Gaulard, Luc Xerri, Gilles Salles, Wolfram Klapper, Michael Phreundschuh, Andrew Jack, Randy D Gascoyne, Yasodha Natkunam, Ranjana Advani, Eva Kimby, Birgitta Sander, Laurie Sehn, Anton Hagenbeek, John Raemaekers, John Gribben, Marie Jose' Kersten, Bauke Ylstra, Edie Weller, Daphne de Jong
In follicular lymphoma, studies addressing the prognostic value of microenvironment-related immunohistochemical markers and tumor cell-related genetic markers have yielded conflicting results, precluding implementation in practice. Therefore, the Lunenburg Lymphoma Biomarker Consortium performed a validation study evaluating published markers. To maximize sensitivity, an end-of-spectrum design was applied for 122 uniformly immunochemotherapy-treated follicular lymphoma patients retrieved from international trials and registries; early failure: progression or lymphoma-related death <2 years versus long remission: response duration of >5 years...
April 14, 2017: Haematologica
https://www.readbyqxmd.com/read/28407694/molecular-mechanisms-of-activating-c-met-in-kshv-primary-effusion-lymphoma
#12
Bao Quoc Lam, Lu Dai, Li Li, Jing Qiao, Zhen Lin, Zhiqiang Qin
The oncogenic Kaposi's sarcoma-associated herpesvirus (KSHV) is a principal causative agent of primary effusion lymphoma (PEL), which is mostly seen in immunosuppressed patients. PEL is a rapidly progressing malignancy with a median survival time of approximately 6 months even under the conventional chemotherapy. We recently report that the hepatocyte growth factor (HGF)/c-MET pathway is highly activated in PEL cells and represents a promising therapeutic target (Blood. 2015;126(26):2821-31). However, the underlying mechanisms of c-MET activation within PEL cells remain largely unknown...
March 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28406802/distinct-subtype-distribution-and-somatic-mutation-spectrum-of-lymphomas-in-east-asia
#13
Weicheng Ren, Wei Li, Xiaofei Ye, Hui Liu, Qiang Pan-Hammarström
PURPOSE OF REVIEW: Here, we give an updated overview of the subtype distribution of lymphomas in East Asia and also present the genome sequencing data on two major subtypes of these tumors. RECENT FINDINGS: The distribution of lymphoma types/subtypes among East Asian countries is very similar, with a lower proportion of B-cell malignancies and a higher proportion of T/natural killer (NK)-cell lymphomas as compared to Western populations. Extranodal NK/T-cell lymphoma is more frequently observed in East Asia, whereas follicular lymphoma and chronic lymphocytic leukemia, are proportionally lower...
April 13, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28405493/hla-class-i-restricted-myd88-l265p-derived-peptides-as-specific-targets-for-lymphoma-immunotherapy
#14
Annika Nelde, Juliane Sarah Walz, Daniel Johannes Kowalewski, Heiko Schuster, Olaf-Oliver Wolz, Janet Kerstin Peper, Yamel Cardona Gloria, Anton W Langerak, Alice F Muggen, Rainer Claus, Irina Bonzheim, Falko Fend, Helmut Rainer Salih, Lothar Kanz, Hans-Georg Rammensee, Stefan Stevanović, Alexander N R Weber
Genome sequencing has uncovered an array of recurring somatic mutations in different non-Hodgkin lymphoma (NHL) subtypes. If affecting protein-coding regions, such mutations may yield mutation-derived peptides that may be presented by HLA class I proteins and recognized by cytotoxic T cells. A recurring somatic and oncogenic driver mutation of the Toll-like receptor adaptor protein MYD88, Leu265Pro (L265P) was identified in up to 90% of different NHL subtype patients. We therefore screened the potential of MYD88(L265P)-derived peptides to elicit cytotoxic T cell responses as tumor-specific neoantigens...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28400759/human-and-epstein-barr-virus-mirna-profiling-as-predictive-biomarkers-for-endemic-burkitt-lymphoma
#15
Cliff I Oduor, Mercedeh Movassagh, Yasin Kaymaz, Kiprotich Chelimo, Juliana Otieno, John M Ong'echa, Ann M Moormann, Jeffrey A Bailey
Endemic Burkitt lymphoma (eBL) is an aggressive B cell lymphoma and is associated with Epstein-Barr virus (EBV) and Plasmodium falciparum malaria co-infections. Central to BL oncogenesis is the over-expression of the MYC proto-oncogene which is caused by a translocation of an Ig enhancer in approximation to the myc gene. While whole genome/transcriptome sequencing methods have been used to define driver mutations and transcriptional dysregulation, microRNA (miRNA) dysregulation and differential expression has yet to be fully characterized...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28393412/early-stages-in-the-ontogeny-of-small-b-cell-lymphomas-genetics-and-microenvironment
#16
P Ghia, B Nadel, B Sander, K Stamatopoulos, F K Stevenson
In this review, we focus on the mechanisms underlying lymphomagenesis in chronic lymphocytic leukaemia, follicular lymphoma, mantle cell lymphoma and splenic marginal zone lymphoma. The cells of origin of these small B-cell lymphomas are distinct, as are the characteristic chromosomal lesions and clinical courses. One shared feature is retention of expression of surface immunoglobulin. Analysis of this critical receptor reveals the point of differentiation reached by the cell of origin. Additionally, the sequence patterns of the immunoglobulin-variable domains can indicate a role for stimulants of the B-cell receptor before, during and after malignant transformation...
April 10, 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/28379322/international-working-group-consensus-response-evaluation-criteria-in-lymphoma-recil-2017
#17
A Younes, P Hilden, B Coiffier, A Hagenbeek, G Salles, W Wilson, J F Seymour, K Kelly, J Gribben, M Pfreunschuh, F Morschhauser, H Schoder, A D Zelenetz, J Rademaker, R Advani, N Valente, C Fortpied, T E Witzig, L H Sehn, A Engert, R I Fisher, P-L Zinzani, M Federico, M Hutchings, C Bollard, M Trneny, Y A Elsayed, K Tobinai, J S Abramson, N Fowler, A Goy, M Smith, S Ansell, J Kuruvilla, M Dreyling, C Thieblemont, R F Little, I Aurer, M H J Van Oers, K Takeshita, A Gopal, S Rule, S de Vos, I Kloos, M S Kaminski, M Meignan, L H Schwartz, J P Leonard, S J Schuster, V E Seshan
In recent years, the number of approved and investigational agents that can be safely administered for the treatment of lymphoma patients for a prolonged period of time has substantially increased. Many of these novel agents are evaluated in early-phase clinical trials in patients with a wide range of malignancies, including solid tumors and lymphoma. Furthermore, with the advances in genome sequencing, new "basket" clinical trial designs have emerged that select patients based on the presence of specific genetic alterations across different types of solid tumors and lymphoma...
April 3, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28376405/dna-methyltransferase-1-mediated-aberrant-methylation-and-silencing-of-shp-1-gene-in-chronic-myelogenous-leukemia-cells
#18
Yinghua Li, Xuedong Liu, Xiufeng Guo, Xiao Liu, Jianmin Luo
INTRODUCTION: Extensive studies on SHP-1 protein and SHP-1 mRNA revealed that the diminishment or abolishment of the expression of SHP-1 in leukemias/lymphomas was due to aberrant promoter methylation. Thus far, the mechanism of epigenetic silencing of the SHP-1 tyrosine phosphatase gene that occurs in chronic myelogenous leukemia cells remains poorly understood. METHODS: The expressions of the target molecules were determined by quantitative real time PCR and western blot, respectively...
March 25, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28376230/target-and-agent-prioritization-for-the-children-s-oncology-group-national-cancer-institute-pediatric-match-trial
#19
Carl E Allen, Theodore W Laetsch, Rajen Mody, Meredith S Irwin, Megan S Lim, Peter C Adamson, Nita L Seibel, D Williams Parsons, Y Jae Cho, Katherine Janeway
Over the past decades, outcomes for children with cancer have improved dramatically through serial clinical trials based in large measure on dose intensification of cytotoxic chemotherapy for children with high-risk malignancies. Progress made through such dose intensification, in general, is no longer yielding further improvements in outcome. With the revolution in sequencing technologies and rapid development of drugs that block specific proteins and pathways, there is now an opportunity to improve outcomes for pediatric cancer patients through mutation-based targeted therapeutic strategies...
May 1, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28362236/nonenhancing-peritumoral-hyperintense-lesion-on-diffusion-weighted-imaging-in-glioblastoma-a-novel-diagnostic-and-specific-prognostic-indicator
#20
Manish Kolakshyapati, Rupendra B Adhikari, Vega Karlowee, Takeshi Takayasu, Ryo Nosaka, Vishwa J Amatya, Yukio Takeshima, Yuji Akiyama, Kazuhiko Sugiyama, Kaoru Kurisu, Fumiyuki Yamasaki
OBJECTIVE Glioblastoma differentials include intracranial tumors, like malignant lymphomas and metastatic brain tumors with indiscernible radiological characteristics. The purpose of this study was to identify a distinct radiological feature for the preoperative differentiation of glioblastoma from its differentials, which include malignant lymphomas and metastatic brain tumors. METHODS Preoperative MR images, including diffusion-weighted imaging (DWI) studies (b = 1000 and 4000 sec/mm(2)), obtained in patients with newly diagnosed malignant tumor, were analyzed retrospectively after receiving approval from the institutional review board...
March 31, 2017: Journal of Neurosurgery
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