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https://www.readbyqxmd.com/read/28088512/ros1-fusions-rarely-overlap-with-other-oncogenic-drivers-in-non-small-cell-lung-cancer
#1
Jessica J Lin, Lauren L Ritterhouse, Siraj M Ali, Mark Bailey, Alexa B Schrock, Justin F Gainor, Lorin A Ferris, Mari Mino-Kenudson, Vincent A Miller, Anthony J Iafrate, Jochen K Lennerz, Alice T Shaw
INTRODUCTION: Chromosomal rearrangements involving the ROS proto-oncogene 1 receptor tyrosine kinase gene (ROS1) define a distinct molecular subset of non-small cell lung cancer (NSCLC) with sensitivity to ROS1 inhibitors. Recent reports have suggested a significant overlap between ROS1 fusions and other oncogenic driver alterations, including mutations in epidermal growth factor receptor (EGFR) and KRAS proto-oncogene (KRAS). METHODS: We identified patients at our institution with ROS1-rearranged NSCLC who had undergone testing for genetic alterations in additional oncogenes, including EGFR, KRAS, and anaplastic lymphoma kinase (ALK)...
January 11, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28074419/deciphering-the-molecular-mechanisms-involved-in-hiv-associated-lipoatrophy-by-transcriptomics-a-pilot-study
#2
Patricia Pérez-Matute, María Iñiguez, Emma Recio-Fernández, José-Antonio Oteo
HIV-associated lipoatrophy (LA) has considerable implications for risk of metabolic diseases, quality of life, and adherence to treatments. Although it has decreased in high-income countries, it is still very common in resource-limited countries. Understanding the pathophysiological mechanisms of LA can open the possibility to explore new ways to treat or prevent this condition. To identify new markers for an accurate and quick diagnosis will be also of interest. Thus, we aimed to examine functional classes of genes implicated in LA and to identify potential new markers for an accurate/quick diagnosis of LA and future complications...
January 10, 2017: Journal of Physiology and Biochemistry
https://www.readbyqxmd.com/read/28068180/clonal-hematopoiesis-associated-with-adverse-outcomes-after-autologous-stem-cell-transplantation-for-lymphoma
#3
Christopher J Gibson, R Coleman Lindsley, Vatche Tchekmedyian, Brenton G Mar, Jiantao Shi, Siddhartha Jaiswal, Alysia Bosworth, Liton Francisco, Jianbo He, Anita Bansal, Elizabeth A Morgan, Ann S Lacasce, Arnold S Freedman, David C Fisher, Eric Jacobsen, Philippe Armand, Edwin P Alyea, John Koreth, Vincent Ho, Robert J Soiffer, Joseph H Antin, Jerome Ritz, Sarah Nikiforow, Stephen J Forman, Franziska Michor, Donna Neuberg, Ravi Bhatia, Smita Bhatia, Benjamin L Ebert
Purpose Clonal hematopoiesis of indeterminate potential (CHIP) is an age-related condition characterized by somatic mutations in the blood of otherwise healthy adults. We hypothesized that in patients undergoing autologous stem-cell transplantation (ASCT) for lymphoma, CHIP at the time of ASCT would be associated with an increased risk of myelodysplastic syndrome and acute myeloid leukemia, collectively termed therapy-related myeloid neoplasm (TMN), and other adverse outcomes. Methods We performed whole-exome sequencing on pre- and post-ASCT samples from 12 patients who developed TMN after autologous transplantation for Hodgkin lymphoma or non-Hodgkin lymphoma and targeted sequencing on cryopreserved aliquots of autologous stem-cell products from 401 patients who underwent ASCT for non-Hodgkin lymphoma between 2003 and 2010...
January 9, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28067225/hepatitis-c-virus-has-a-genetically-determined-lymphotropism-through-co-receptor-b7-2
#4
Chia-Lin Chen, Jeffrey Y Huang, Chun-Hsiang Wang, Stanley M Tahara, Lin Zhou, Yasuteru Kondo, Joel Schechter, Lishan Su, Michael M C Lai, Takaji Wakita, François-Loïc Cosset, Jae U Jung, Keigo Machida
B-cell infection by hepatitis C virus (HCV) has been a controversial topic. To examine whether HCV has a genetically determined lymphotropism through a co-receptor specific for the infection by lymphotropic HCV, we established an infectious clone and chimeric virus of hepatotropic and lymphotropic HCV strains derived from an HCV-positive B-cell lymphoma. The viral envelope and 5'-UTR sequences of the lymphotropic HCV strain were responsible for the lymphotropism. Silencing of the virus sensor, RIGI, or overexpression of microRNA-122 promoted persistent viral replication in B cells...
January 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28065229/detection-of-echinoderm-microtubule-associated-protein-like-4-anaplastic-lymphoma-kinase-fusion-genes-in-non-small-cell-lung-cancer-clinical-samples-by-a-real-time-quantitative-reverse-transcription-polymerase-chain-reaction-method
#5
Jing Zhao, Jin-Yin Zhao, Zhi-Xia Chen, Wei Zhong, Long-Yun Li, Li-Cheng Liu, Xiao-Xu Hu, Wei-Jun Chen, Meng-Zhao Wang
Objective To establish a real-time quantitative reverse transcription polymerase chain reaction assay (qRT-PCR) for the rapid, sensitive, and specific detection of echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) fusion genes in non-small cell lung cancer. Methods The specific primers for the four variants of EML4-ALK fusion genes (V1, V2, V3a, and V3b) and Taqman fluorescence probes for the detection of the target sequences were carefully designed by the Primer Premier 5...
December 20, 2016: Zhongguo Yi Xue Ke Xue Yuan Xue Bao. Acta Academiae Medicinae Sinicae
https://www.readbyqxmd.com/read/28064239/recurrent-somatic-mutations-affecting-b-cell-receptor-signaling-pathway-genes-in-follicular-lymphoma
#6
Kilannin Krysiak, Felicia Gomez, Brian S White, Matthew Matlock, Christopher A Miller, Lee Trani, Catrina C Fronick, Robert S Fulton, Friederike Kreisel, Amanda F Cashen, Kenneth R Carson, Melissa M Berrien-Elliott, Nancy L Bartlett, Malachi Griffith, Obi L Griffith, Todd A Fehniger
Follicular lymphoma (FL) is the most common form of indolent non-Hodgkin lymphoma, yet it remains only partially characterized at the genomic level. In order to improve our understanding of the genetic underpinnings of this incurable and clinically heterogeneous disease, whole exome sequencing was performed on tumor/normal pairs from a discovery cohort of 24 patients with FL. Using these data, and mutations identified in other B-cell malignancies, 1716 genes were sequenced in 113 FL tumor samples, from 105 primarily treatment-naïve individuals...
November 14, 2016: Blood
https://www.readbyqxmd.com/read/28062691/activating-mutations-and-translocations-in-the-guanine-exchange-factor-vav1-in-peripheral-t-cell-lymphomas
#7
Francesco Abate, Ana C da Silva-Almeida, Sakellarios Zairis, Javier Robles-Valero, Lucile Couronne, Hossein Khiabanian, S Aidan Quinn, Mi-Yeon Kim, Maria Antonella Laginestra, Christine Kim, Danilo Fiore, Govind Bhagat, Miguel Angel Piris, Elias Campo, Izidore S Lossos, Olivier A Bernard, Giorgio Inghirami, Stefano Pileri, Xosé R Bustelo, Raul Rabadan, Adolfo A Ferrando, Teresa Palomero
Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of non-Hodgkin lymphomas frequently associated with poor prognosis and for which genetic mechanisms of transformation remain incompletely understood. Using RNA sequencing and targeted sequencing, here we identify a recurrent in-frame deletion (VAV1 Δ778-786) generated by a focal deletion-driven alternative splicing mechanism as well as novel VAV1 gene fusions (VAV1-THAP4, VAV1-MYO1F, and VAV1-S100A7) in PTCL. Mechanistically these genetic lesions result in increased activation of VAV1 catalytic-dependent (MAPK, JNK) and non-catalytic-dependent (nuclear factor of activated T cells, NFAT) VAV1 effector pathways...
January 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28060738/the-prognostic-value-of-clonal-heterogeneity-and-quantitative-assessment-of-plasma-circulating-clonal-ig-vdj-sequences-at-diagnosis-in-patients-with-follicular-lymphoma
#8
Clémentine Sarkozy, Sarah Huet, Victoria E H Carlton, Bettina Fabiani, Alain Delmer, Fabrice Jardin, Marie-Helene Delfau-Larue, Maya Hacini, Vincent Ribrag, Stéphanie Guidez, Malek Faham, Gilles Salles
Recent advances in next-generation sequencing (NGS) have enabled the quantitation of circulating tumour DNA (ctDNA) encoding the clonal rearranged V(D)J immunoglobulin locus. We aimed to evaluate the clonal heterogeneity of follicular lymphoma (FL) in the tumour and the plasma at diagnosis and to assess the prognostic value of the ctDNA level. Plasma samples at diagnosis were available for 34 patients registered in the PRIMA trial (NCT00140582). One tumour clonotype or more could be detected for 29 (85%) and 25 (74%) patients, respectively, in the tumour or plasma samples...
January 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28042684/detection-of-the-myd88-mutation-by-the-combination-of-the-allele-specific-pcr-and-quenching-probe-methods
#9
S Nogami, N Kawaguchi-Ihara, E Shiratori, M Ohtaka, M Itoh, S Tohda
INTRODUCTION: The MYD88 missense mutation c.794T>C, p.Leu265Pro, is found in patients with Waldenstörm's macroglobulinemia and lymphoma. Direct sequencing, allele-specific PCR (AS-PCR), PCR-restriction fragment length polymorphism (PCR-RFLP), and high-resolution melting analysis (HRM) are currently used to detect the mutation; however, they are either time-consuming or have low detection sensitivity. Here, we developed a novel highly sensitive and rapid detection method based on the quenching probe (QP) technique and AS-PCR...
January 1, 2017: International Journal of Laboratory Hematology
https://www.readbyqxmd.com/read/28038319/recruitment-of-tiam1-to-semaphorin-4d-activates-rac-and-enhances-proliferation-invasion-and-metastasis-in-oral-squamous-cell-carcinoma
#10
Hua Zhou, Maricel G Kann, Emily K Mallory, Ying-Hua Yang, Amr Bugshan, Nada O Binmadi, John R Basile
The semaphorins and the plexins are a family of large, cysteine-rich proteins originally identified as regulators of axon growth and lymphocyte activation that are now known to provide motility and positional information for a number of cell and tissue types. For example, our group and others have shown that some malignancies over express Semaphorin 4D (S4D), which acts through its receptor Plexin-B1 (PB1) on endothelial cells to attract blood vessels from the surrounding stroma for the purpose of supporting tumor growth...
December 27, 2016: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28034804/whole-body-clonality-analysis-in-an-aggressive-stlv-1-associated-leukemia-atll-reveals-an-unexpected-clonal-complexity
#11
Jocelyn Turpin, Sandrine Alais, Ambroise Marçais, Julie Bruneau, Anat Melamed, Nicolas Gadot, Yuetsu Tanaka, Olivier Hermine, Sandrine Melot, Romain Lacoste, Charles R Bangham, Renaud Mahieux
HTLV-1 causes Adult T cell Leukemia/Lymphoma (ATLL) in humans. We describe an ATL-like disease in a 9 year-old female baboon naturally infected with STLV-1 (the simian counterpart of HTLV-1), with a lymphocyte count over 10(10)/L, lymphocytes with abnormal nuclear morphology, and pulmonary and skin lesions. The animal was treated with a combination of AZT and alpha interferon. Proviral load (PVL) was measured every week. Because the disease continued to progress, the animal was euthanized. Abnormal infiltrates of CD3(+)CD25(+) lymphocytes and Tax-positive cells were found by histological analyses in both lymphoid and non-lymphoid organs...
December 26, 2016: Cancer Letters
https://www.readbyqxmd.com/read/28034318/sensitive-and-precise-characterization-of-combinatorial-histone-modifications-by-selective-derivatization-coupled-with-rplc-ethcd-ms-ms
#12
Rijing Liao, Dan Zheng, Aiying Nie, Shaolian Zhou, Haibing Deng, Yuan Gao, Pengyuan Yang, Yanyan Yu, Lin Tan, Wei Qi, Jiaxi Wu, En Li, Wei Yi
Deciphering the combinatorial histone codes has been a long-standing interest in the epigenetics field, which requires the reliable and robust characterization of the post-translational modifications (PTMs) coexisting on histones. To this end, weak cation exchange hydrophilic interaction liquid chromatography is commonly used in middle-down liquid chromatography-mass spectrometry approaches for online separation of variously modified histone peptides. Here we provide a novel strategy that combines the selective histone peptide derivatization using N-hydroxysuccinimide propionate ester with reversed-phase liquid chromatography (RPLC) for the robust, sensitive, and reliable characterization of combinatorial histone PTMs...
January 11, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28031173/preference-for-subcutaneous-or-intravenous-administration-of-rituximab-among-patients-with-untreated-cd20-diffuse-large-b-cell-lymphoma-or-follicular-lymphoma-results-from-a-prospective-randomized-open-label-crossover-study-prefmab
#13
M Rummel, T M Kim, F Aversa, W Brugger, E Capochiani, C Plenteda, F Re, P Trask, S Osborne, R Smith, A Grigg
BACKGROUND: To evaluate patient preference and satisfaction for the subcutaneous (SC) versus intravenous (IV) formulation of rituximab given with chemotherapy in previously untreated patients with CD20+ diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL). PATIENTS AND METHODS: Patients received 8 cycles of rituximab according to 2 schedules: Arm A received 1 cycle rituximab IV (375 mg/m(2)) and 3 cycles rituximab SC (1400 mg) then 4 cycles rituximab IV; Arm B received 4 cycles rituximab IV (375 mg/m(2)) then 4 cycles rituximab SC (1400 mg)...
December 28, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28028120/ccnd1-igh-fusion-amplification-and-myc-copy-number-gain-in-a-case-of-pleomorphic-variant-mantle-cell-lymphoma
#14
Yuan Miao, Pei Lin, Wei Wang, L Jeffrey Medeiros, Xinyan Lu
OBJECTIVES: Mantle cell lymphoma (MCL) may present de novo or undergo progression to a clinically aggressive variant, known as a blastoid or pleomorphic variant. We report an unusual case of classic MCL in a 78-year-old man with a typical immunophenotype, including CD5 positivity, who subsequently relapsed with CD5-negative pleomorphic variant MCL. METHODS: Biopsy specimens were evaluated using Wright-Giemsa-stained or H&E-stained sections, flow cytometry, immunohistochemistry, conventional cytogenetic, next-generation sequencing, and fluorescence in situ hybridization...
December 27, 2016: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28024916/drug-free-macromolecular-therapeutics-impact-of-structure-on-induction-of-apoptosis-in-raji-b-cells
#15
Libin Zhang, Yixin Fang, Jiyuan Yang, Jindřich Kopeček
Recently, we developed a new paradigm in macromolecular therapeutics that avoids the use of low molecular weight drugs. The activity of the "drug-free macromolecular therapeutics" is based on the biorecognition of complementary motifs at cell surface resulting in receptor crosslinking and apoptosis induction. The system is composed of two nanoconjugates: (1) a single-stranded morpholino oligonucleotide (MORF1) attached to an anti-CD20 Fab' fragment (Fab'-MORF1); (2) multiple copies of complementary oligonucleotide MORF2 grafted to a linear polymer of N-(2-hydroxypropyl)methacrylamide (HPMA) - P-(MORF2)x...
December 23, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28018601/the-society-for-immunotherapy-of-cancer-consensus-statement-on-immunotherapy-for-the-treatment-of-hematologic-malignancies-multiple-myeloma-lymphoma-and-acute-leukemia
#16
Michael Boyiadzis, Michael R Bishop, Rafat Abonour, Kenneth C Anderson, Stephen M Ansell, David Avigan, Lisa Barbarotta, Austin John Barrett, Koen Van Besien, P Leif Bergsagel, Ivan Borrello, Joshua Brody, Jill Brufsky, Mitchell Cairo, Ajai Chari, Adam Cohen, Jorge Cortes, Stephen J Forman, Jonathan W Friedberg, Ephraim J Fuchs, Steven D Gore, Sundar Jagannath, Brad S Kahl, Justin Kline, James N Kochenderfer, Larry W Kwak, Ronald Levy, Marcos de Lima, Mark R Litzow, Anuj Mahindra, Jeffrey Miller, Nikhil C Munshi, Robert Z Orlowski, John M Pagel, David L Porter, Stephen J Russell, Karl Schwartz, Margaret A Shipp, David Siegel, Richard M Stone, Martin S Tallman, John M Timmerman, Frits Van Rhee, Edmund K Waller, Ann Welsh, Michael Werner, Peter H Wiernik, Madhav V Dhodapkar
Increasing knowledge concerning the biology of hematologic malignancies as well as the role of the immune system in the control of these diseases has led to the development and approval of immunotherapies that are resulting in impressive clinical responses. Therefore, the Society for Immunotherapy of Cancer (SITC) convened a hematologic malignancy Cancer Immunotherapy Guidelines panel consisting of physicians, nurses, patient advocates, and patients to develop consensus recommendations for the clinical application of immunotherapy for patients with multiple myeloma, lymphoma, and acute leukemia...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28007627/clinical-outcome-of-alk-positive-non-small-cell-lung-cancer-nsclc-patients-with-de-novo-egfr-or-kras-co-mutations-receiving-tyrosine-kinase-inhibitors-tki
#17
Sabine Schmid, Oliver Gautschi, Sacha Rothschild, Michael Mark, Patrizia Froesch, Dirk Klingbiel, Hermann Reichegger, Wolfram Jochum, Joachim Diebold, Früh Martin
BACKGROUND: Non-small cell lung cancer (NSCLC) with de novo anaplastic lymphoma kinase (ALK) rearrangements and epidermal growth factor receptor (EGFR) or Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations co-occur very rarely. Outcomes with tyrosine kinase inhibitors (TKIs) in these patients (pts) are poorly understood. METHODS: Outcomes of pts with metastatic NSCLC de novo co- alterations of ALK/EGFR or ALK/KRAS detected by FISH (ALK) and sequencing (EGFR/KRAS) from six Swiss centres were analysed...
December 19, 2016: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28005210/akt-capture-by-feline-leukemia-virus
#18
Maki Kawamura, Daigo Umehara, Yuka Odahara, Ariko Miyake, Minh Ha Ngo, Yoshiharu Ohsato, Masaharu Hisasue, Masa-Aki Nakaya, Shinya Watanabe, Kazuo Nishigaki
Oncogene-containing retroviruses are generated by recombination events between viral and cellular sequences, a phenomenon called "oncogene capture". The captured cellular genes, referred to as "v-onc" genes, then acquire new oncogenic properties. We report a novel feline leukemia virus (FeLV), designated "FeLV-AKT", that has captured feline c-AKT1 in feline lymphoma. FeLV-AKT contains a gag-AKT fusion gene that encodes the myristoylated Gag matrix protein and the kinase domain of feline c-AKT1, but not its pleckstrin homology domain...
December 22, 2016: Archives of Virology
https://www.readbyqxmd.com/read/28003262/defining-the-clonality-of-peripheral-t-cell-lymphomas-using-rna-seq
#19
Scott D Brown, Greg Hapgood, Christian Steidl, Andrew P Weng, Kerry J Savage, Robert A Holt
MOTIVATION: In T-cell lymphoma, malignant T cells arising from a founding clone share an identical T cell receptor (TCR) and can be identified by the over-representation of this TCR relative to TCRs from the patient's repertoire of normal T cells. Here, we demonstrate that TCR information extracted from RNA-seq data can provide a higher resolution view of peripheral T cell lymphomas (PTCLs) than that provided by conventional methods. RESULTS: For 60 subjects with PTCL, flow cytometry/FACS was used to identify and sort aberrant T cell populations from diagnostic lymph node cell suspensions...
December 21, 2016: Bioinformatics
https://www.readbyqxmd.com/read/28002793/next-generation-sequencing-of-vitreoretinal-lymphomas-from-small-volume-intraocular-liquid-biopsies-new-routes-to-targeted-therapies
#20
Andi K Cani, Daniel H Hovelson, Hakan Demirci, Mark W Johnson, Scott A Tomlins, Rajesh C Rao
BACKGROUND: Vitreoretinal lymphoma (VRL), the most common lymphoma of the eye, is a rare form of primary CNS lymphoma (PCNSL). Most frequently a high-grade diffuse large B cell lymphoma, VRL can cause vision loss and its prognosis remains dismal: the overall survival time is 3 years after diagnosis. Radiotherapy and chemotherapy are used but remain frequently ineffective, and no standardized treatment regimen exists. Furthermore, no biologically targeted treatments, based on the genetic profile of the tumor, are available, as VRL has hitherto not comprehensively been profiled...
December 17, 2016: Oncotarget
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