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Genomic lymphoma

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https://www.readbyqxmd.com/read/28646116/tonic-b-cell-receptor-signaling-in-diffuse-large-b-cell-lymphoma
#1
Ondrej Havranek, Jingda Xu, Stefan Köhrer, Zhiqiang Wang, Lisa Becker, Justin M Comer, Jared Henderson, Wencai Ma, John Man Chun Ma, Jason R Westin, Dipanjan Ghosh, Nicholas Shinners, Luhong Sun, Allen F Yi, Anusha R Karri, Jan A Burger, Tomasz Zal, R Eric Davis
We used CRISPR/Cas9-mediated genomic modification to investigate B-cell receptor (BCR) signaling in cell lines of diffuse large B-cell lymphoma (DLBCL). Three manipulations that altered BCR genes without affecting surface BCR levels showed that BCR signaling differs between the germinal center B-cell (GCB) subtype, which is insensitive to BTK inhibition by ibrutinib, and the activated B-cell (ABC) subtype. Replacing antigen-binding BCR regions had no effect on BCR signaling in GCB-DLBCL lines, reflecting this subtype's exclusive use of tonic BCR signaling...
June 23, 2017: Blood
https://www.readbyqxmd.com/read/28644837/real-world-first-line-treatment-and-overall-survival-in-non-small-cell-lung-cancer-without-known-egfr-mutations-or-alk-rearrangements-in-us-community-oncology-setting
#2
Amy P Abernethy, Ashwini Arunachalam, Thomas Burke, Caroline McKay, Xiting Cao, Rachael Sorg, David P Carbone
PURPOSE: To establish a baseline for care and overall survival (OS) based upon contemporary first-line treatments prescribed in the era before the introduction of immune checkpoint inhibitors, for people with metastatic non-small cell lung cancer (NSCLC) without common actionable mutations. METHODS: Using a nationally representative electronic health record data from the Flatiron dataset which included 162 practices from different regions in US, we identified patients (≥18 years old) newly diagnosed with stage IV NSCLC initiating first-line anticancer therapy (November 2012- January 2015, with follow-up through July 2015)...
2017: PloS One
https://www.readbyqxmd.com/read/28644138/comparative-analysis-of-primary-versus-relapse-refractory-dlbcl-identifies-shifts-in-mutation-spectrum
#3
Danielle M Greenawalt, Winnie S Liang, Sakina Saif, Justin Johnson, Petar Todorov, Austin Dulak, Daniel Enriquez, Rebecca Halperin, Ambar Ahmed, Vladislav Saveliev, John Carpten, David Craig, J Carl Barrett, Brian Dougherty, Michael Zinda, Stephen Fawell, Jonathan R Dry, Kate Byth
Current understanding of the mutation spectrum of relapsed/refractory (RR) tumors is limited. We performed whole exome sequencing (WES) on 47 diffuse large B cell lymphoma (DLBCL) tumors that persisted after R-CHOP treatment, 8 matched to primary biopsies. We compared genomic alterations from the RR cohort against two treatment-naïve DLBCL cohorts (n=112). While the overall number and types of mutations did not differ significantly, we identified frequency changes in DLBCL driver genes. The overall frequency of MYD88 mutant samples increased (12% to 19%), but we noted a decrease in p...
June 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28637474/arsenic-trioxide-inhibits-ebv-reactivation-and-promotes-cell-death-in-ebv-positive-lymphoma-cells
#4
Qinyan Yin, Mark Sides, Christopher H Parsons, Erik K Flemington, Joseph A Lasky
BACKGROUND: Epstein-Barr Virus (EBV) is associated with hematopoietic malignancies, such as Burkitt's lymphoma, post-transplantation lymphoproliferative disorder, and diffuse large B-cell lymphoma. The current approach for EBV-associated lymphoma involves chemotherapy to eradicate cancer cells, however, normal cells may be injured and organ dysfunction may occur with currently employed regimens. This research is focused on employing arsenic trioxide (ATO) as EBV-specific cancer therapy takes advantage of the fact the EBV resides within the malignant cells...
June 21, 2017: Virology Journal
https://www.readbyqxmd.com/read/28636991/non-invasive-detection-of-somatic-mutations-using-next-generation-sequencing-in-primary-central-nervous-system-lymphoma
#5
Maxime Fontanilles, Florent Marguet, Élodie Bohers, Pierre-Julien Viailly, Sydney Dubois, Philippe Bertrand, Vincent Camus, Sylvain Mareschal, Philippe Ruminy, Catherine Maingonnat, Stéphane Lepretre, Elena-Liana Veresezan, Stéphane Derrey, Hervé Tilly, Jean-Michel Picquenot, Annie Laquerrière, Fabrice Jardin
PURPOSE: Primary central nervous system lymphomas (PCNSL) have recurrent genomic alterations. The main objective of our study was to demonstrate that targeted sequencing of circulating cell-free DNA (cfDNA) released by PCNSL at the time of diagnosis could identify somatic mutations by next-generation sequencing (NGS). PATIENTS AND METHODS: PlasmacfDNA and matched tumor DNA (tDNA) from 25 PCNSL patients were sequenced using an Ion Torrent Personal Genome Machine (Life Technologies®)...
June 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28630229/observing-clonal-dynamics-across-spatiotemporal-axes-a-prelude-to-quantitative-fitness-models-for-cancer
#6
Andrew W McPherson, Fong Chun Chan, Sohrab P Shah
The ability to accurately model evolutionary dynamics in cancer would allow for prediction of progression and response to therapy. As a prelude to quantitative understanding of evolutionary dynamics, researchers must gather observations of in vivo tumor evolution. High-throughput genome sequencing now provides the means to profile the mutational content of evolving tumor clones from patient biopsies. Together with the development of models of tumor evolution, reconstructing evolutionary histories of individual tumors generates hypotheses about the dynamics of evolution that produced the observed clones...
June 19, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/28625332/considerations-of-developing-an-ngs-assay-for-clinical-applications-in-precision-oncology-the-nci-match-ngs-assay-experience
#7
Chih-Jian Lih, Naoko Takebe
Next generation sequencing (NGS) technologies have been widely adapted in clinical oncology by utilizing the profiled genetic mutation information to select patients and to guide the choice of target therapy. To fulfill the regulatory compliance, development of an NGS assay that will be used in clinical trials requires an analytical validation to meet its intend clinical use. NCI-MATCH trial is the largest precision oncology basket trial which uses a single NGS assay (NCI-MATHC NGS assay) to screen the actionable mutations in 6000 patients, who have relapsed/refractory solid tumors and lymphomas after standard systemic treatment, and assigns matched treatment...
May 2017: Current Problems in Cancer
https://www.readbyqxmd.com/read/28608966/next-generation-sequencing-and-clinical-outcomes-of-patients-with-lung-adenocarcinoma-treated-with-stereotactic-body-radiotherapy
#8
Richard J Cassidy, Xinyan Zhang, Pretesh R Patel, Joseph W Shelton, Chase E Escott, Gabriel L Sica, Michael R Rossi, Charles E Hill, Conor E Steuer, Rathi N Pillai, Suresh S Ramalingam, Taofeek K Owonikoko, Madhusmita Behera, Seth D Force, Felix G Fernandez, Walter J Curran, Kristin A Higgins
BACKGROUND: Genetic aberrations are well characterized in lung adenocarcinomas (LACs) and clinical outcomes have been influenced by targeted therapies in the advanced setting. Stereotactic body radiotherapy (SBRT) is the standard-of-care therapy for patients with nonoperable, early-stage LAC, but to the authors' knowledge, no information is available regarding the impact of genomic changes in these patients. The current study sought to determine the frequency and clinical impact of genetic aberrations in this population...
June 13, 2017: Cancer
https://www.readbyqxmd.com/read/28607076/functional-proteogenomics-reveals-biomarkers-and-therapeutic-targets-in-lymphomas
#9
Delphine C M Rolland, Venkatesha Basrur, Yoon-Kyung Jeon, Carla McNeil-Schwalm, Damian Fermin, Kevin P Conlon, Yeqiao Zhou, Samuel Y Ng, Chih-Chiang Tsou, Noah A Brown, Dafydd G Thomas, Nathanael G Bailey, Gilbert S Omenn, Alexey I Nesvizhskii, David E Root, David M Weinstock, Robert B Faryabi, Megan S Lim, Kojo S J Elenitoba-Johnson
Identification of biomarkers and therapeutic targets is a critical goal of precision medicine. N-glycoproteins are a particularly attractive class of proteins that constitute potential cancer biomarkers and therapeutic targets for small molecules, antibodies, and cellular therapies. Using mass spectrometry (MS), we generated a compendium of 1,091 N-glycoproteins (from 40 human primary lymphomas and cell lines). Hierarchical clustering revealed distinct subtype signatures that included several subtype-specific biomarkers...
June 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28600336/diagnosis-and-classification-of-hematologic-malignancies-on-the-basis-of-genetics
#10
Justin Taylor, Wenbin Xiao, Omar Abdel-Wahab
Genomic analysis has greatly influenced the diagnosis and clinical management of patients affected by diverse forms of hematologic malignancies. Here we review how genetic alterations define subclasses of patients with acute leukemias, myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPNs), non-Hodgkin lymphomas and classical Hodgkin lymphoma. These include new subtypes of acute myeloid leukemia defined by mutations in RUNX1 or BCR-ABL1 translocations as well as a constellation of somatic structural DNA alterations in acute lymphoblastic leukemia...
June 9, 2017: Blood
https://www.readbyqxmd.com/read/28596939/undifferentiated-pleomorphic-sarcoma-and-the-importance-of-considering-the-oncogenic-and-immune-suppressant-role-of-the-human-t-cell-lymphotropic-virus-type-1-a-case-report
#11
Sergio Lupo, Carolina Berini, Camila Cánepa, Eduardo Santini Araujo, Mirna Biglione
INTRODUCTION: Soft-tissue sarcomas account for 0.7% of all malignant tumors, with an incidence rate of 3 per 100,000 persons/year. The undifferentiated pleomorphic sarcoma (UPS) with giant cells, a high grade tumor of soft tissue, is very unusual, especially in young adults before the age of 40. Human T-cell lymphotropic virus type 1 (HTLV-1) is a human retrovirus, classified as group 1 human carcinogens by The International Agency for Research on Cancer, that causes an aggressive malignancy known as adult T-cell lymphoma/leukemia and a progressive chronic inflammatory neurological disease named HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP)...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28590426/down-s-syndrome-and-triple-negative-breast-cancer-a-rare-occurrence-of-distinctive-clinical-relationship
#12
Nandini Dey, Amy Krie, Jessica Klein, Kirstin Williams, Amanda McMillan, Rachel Elsey, Yuliang Sun, Casey Williams, Pradip De, Brian Leyland-Jones
Down's syndrome (DS), the most common genetic cause of significant intellectual disability in children and adults is caused by the trisomy of either all or a part of human chromosome 21 (HSA21). Patients with DS mostly suffer from characteristic tumor types. Although individual patients of DS are at a higher risk for acute leukemia and testicular cancers, other types of solid tumors including breast cancers are mostly uncommon and have significantly lower-than-expected age-adjusted incidence rates. Except for an increased risk of retinoblastomas, and lymphomas, the risk of developing solid tumors has been found to be lower in both children and adults, and breast cancer was found to be almost absent (Hasle H...
June 7, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28587387/functions-of-endothelin-1-in-apoptosis-and-migration-in-hepatocellular-carcinoma
#13
Lu Shi, Shan-Shan Zhou, Wan-Bo Chen, Lei Xu
Hepatocellular carcinoma (HCC) is the second leading cause of cancer mortality in China and the third leading cause of cancer mortality worldwide. The mechanisms involved in the development and progression of HCC are not well understood. In the present study, the functions of endothelin-1 (ET-1) in HCC were studied and its underlying mechanisms were investigated. ET-1, B-cell lymphoma 2 (Bcl-2), Bcl-2 related protein 4 (Bax), matrix metalloproteinase (MMP)-2 and MMP-9 expression was measured by reverse transcription-quantitative polymerase chain reaction and western blotting...
June 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28580307/liquid-chromatography-mass-spectrometry-based-metabolite-pathway-analyses-of-myeloma-and-non-hodgkin-s-lymphoma-patients
#14
Carl Angelo D Medriano, Jinhyuk Na, Kyung-Min Lim, Jin-Ho Chung, Youngja H Park
OBJECTIVE: This study attempted to identify altered metabolism and pathways related to non-Hodgkin's lymphoma (NHL) and myeloma patients. MATERIALS AND METHODS: In this retrospective study, we collected plasma samples from 11 patients-6 healthy controls with no evidence of any blood cancers and 5 patients with either multiple myeloma (n=3) or NHL (n=2) during the preliminary study period. Samples were analyzed using quadrupole time-of-flight liquid chromatography mass spectrometry (LC-MS)...
2017: Cell Journal
https://www.readbyqxmd.com/read/28561648/tissue-agnostic-drug-development
#15
Keith T Flaherty, Dung T Le, Steven Lemery
The U.S. Food and Drug Administration (FDA) has approved drugs to treat patients with tumor types based on a single anatomic site, such as renal cell carcinoma or melanoma, rather than on a biomarker alone. This standard approach is based on a number of factors, including heterogeneity of drug effects in different biomarker-positive tumor types. Additionally, drug development for some drugs was primarily directed toward a specific genomic abnormality in a specific tumor type (e.g., drugs for anaplastic lymphoma kinase [ALK] fusion-positive non-small cell lung cancer)...
2017: American Society of Clinical Oncology Educational Book
https://www.readbyqxmd.com/read/28561533/emergence-of-bruton-s-tyrosine-kinase-negative-hodgkin-lymphoma-during-ibrutinib-treatment-of-chronic-lymphocytic-leukaemia
#16
Siobhan Glavey, John Quinn, Mary McCloy, Jeremy Sargent, Yvonne McCartney, Mark Catherwood, Teresa Marafioti, Mary Leader, Philip Murphy, Patrick Thornton
Chronic Lymphocytic Leukaemia (CLL) is a chronic B cell lympho-proliferative disorder in which lymphomatous transformations occur in 5-15% of patients. Histologically these cases resemble diffuse large B cell lymphoma, or Richter's transformation, in over 80% of cases. Rare cases of transformation to Hodgkin lymphoma (HL) have been reported in the literature with an estimated prevalence of 0.4%. We report a case of a 67 year-old female with CLL treated with the novel Bruton's tyrosine kinase (Btk) inhibitor, ibrutinib, who subsequently presented with intractable fevers...
May 31, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28558176/primary-vitreoretinal-lymphoma-a-review
#17
Iguaracyra Araujo, Sarah E Coupland
Primary vitreoretinal lymphoma (PVRL) is the most common intraocular lymphoma occurring in the eye. It is a high-grade typically B-cell malignancy, arising in the retina, and is often associated with central nervous system (CNS) disease and thereby a poor prognosis. It needs to be distinguished from choroidal low-grade B-cell lymphomas, which do not disseminate to the brain and have a good prognosis. Because of the rarity of PVRL, information is lacking regarding its true incidence, its geographical or ethnic variation, and underlying risk factors apart from immunosuppression associated with human immunodeficiency virus (HIV) and Epstein Barr virus...
May 2017: Asia-Pacific Journal of Ophthalmology
https://www.readbyqxmd.com/read/28557251/evidence-for-the-association-of-epstein-barr-virus-in-breast-cancer-in-indian-patients-using-in-situ-hybridization-technique
#18
Trupti Pai, Sudeep Gupta, Mamta Gurav, Shona Nag, Tanuja Shet, Asawari Patil, Sangeeta Desai
Epstein-Barr Virus (EBV) is etiologically linked to Burkitt lymphoma (BL), nasopharyngeal carcinoma, post-transplant lymphomas, Hodgkin disease, and possibly other tumors. However, the association of oncogenic EBV with breast carcinoma (BC) is still controversial and a matter of debate. We aimed to study the presence of EBV genome in BC cases in Indian patients and its association with the clinicopathological features. The formalin fixed paraffin embedded tissues from 83 women with primary invasive BC were studied for the presence of EBV by in-situ hybridization (ISH) technique for Epstein-Barr Virus Encoded RNA (EBER) with appropriate controls...
May 30, 2017: Breast Journal
https://www.readbyqxmd.com/read/28554945/genetic-background-and-evolution-of-relapses-in-aggressive-b-cell-lymphomas
#19
Darius Juskevicius, Stephan Dirnhofer, Alexandar Tzankov
Relapses of aggressive B-cell lymphomas pose a higher risk to the affected patients due to potential treatment resistance and usually more aggressive tumor growth. Recent advances, such as targeting Bruton tyrosine kinase showed promising results in small number of cases, however treatment for the majority of patients remains challenging and outcomes are generally poor. Recently, a number of studies were published, which utilized state-of-the-art genomic technologies in an attempt to better understand tumor genome evolution during relapse and identify relapse-specific genetic alterations...
May 29, 2017: Haematologica
https://www.readbyqxmd.com/read/28541439/the-evolutionary-landscape-of-dbl-like-rhogef-families-adapting-eukaryotic-cells-to-environmental-signals
#20
Philippe Fort, Anne Blangy
The dynamics of cell morphology in eukaryotes is largely controlled by small GTPases of the Rho family. Rho GTPases are activated by guanine nucleotide exchange factors (RhoGEFs), of which diffuse B-cell lymphoma (Dbl)-like members form the largest family. Here, we surveyed Dbl-like sequences from 175 eukaryotic genomes and illuminate how the Dbl family evolved in all eukaryotic supergroups. By combining probabilistic phylogenetic approaches and functional domain analysis, we show that the human Dbl-like family is made of 71 members, structured into 20 subfamilies...
June 1, 2017: Genome Biology and Evolution
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