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https://www.readbyqxmd.com/read/29686426/transcript-indexed-atac-seq-for-precision-immune-profiling
#1
Ansuman T Satpathy, Naresha Saligrama, Jason D Buenrostro, Yuning Wei, Beijing Wu, Adam J Rubin, Jeffrey M Granja, Caleb A Lareau, Rui Li, Yanyan Qi, Kevin R Parker, Maxwell R Mumbach, William S Serratelli, David G Gennert, Alicia N Schep, M Ryan Corces, Michael S Khodadoust, Youn H Kim, Paul A Khavari, William J Greenleaf, Mark M Davis, Howard Y Chang
T cells create vast amounts of diversity in the genes that encode their T cell receptors (TCRs), which enables individual clones to recognize specific peptide-major histocompatibility complex (MHC) ligands. Here we combined sequencing of the TCR-encoding genes with assay for transposase-accessible chromatin with sequencing (ATAC-seq) analysis at the single-cell level to provide information on the TCR specificity and epigenomic state of individual T cells. By using this approach, termed transcript-indexed ATAC-seq (T-ATAC-seq), we identified epigenomic signatures in immortalized leukemic T cells, primary human T cells from healthy volunteers and primary leukemic T cells from patient samples...
April 23, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29684201/dysregulation-of-epstein-barr-virus-infection-in-hypomorphic-zap70-mutation
#2
Akihiro Hoshino, Takehiro Takashima, Kenichi Yoshida, Akira Morimoto, Yuta Kawahara, Tzu-Wen Yeh, Tsubasa Okano, Motoi Yamashita, Noriko Mitsuiki, Kohsuke Imai, Takashi Sakatani, Atsuko Nakazawa, Yusuke Okuno, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Satoru Miyano, Seishi Ogawa, Seiji Kojima, Tomohiro Morio, Hirokazu Kanegane
Background: Some patients with genetic defects develop Epstein-Barr virus (EBV)-associated lymphoproliferative disorder (LPD)/lymphoma as the main feature. Hypomophic mutations can cause different clinical and laboratory manifestations from null mutations in the same genes. Methods: We sought to describe the clinical and immunologic phenotype of a 21-month-old boy having EBV-associated LPD who was in good health till then. A genetic and immunologic analysis was performed...
April 19, 2018: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29683819/primary-and-metastatic-melanoma-with-ntrk-fusions
#3
Cecilia Lezcano, Alexander N Shoushtari, Charlotte Ariyan, Travis J Hollmann, Klaus J Busam
A number of oncogenic driver mutations have been identified in melanocytic nevi and melanoma, but translocations also play a role in tumorigenesis and provide potential therapeutic targets for malignant lesions. Various translocations, such as those involving the anaplastic lymphoma kinase (ALK), neurotrophic tropomyosin receptor kinase 1 (NTRK1), and NTRK3 have been reported in spitzoid melanocytic neoplasms leading to kinase-fusion proteins that result in immunohistochemically detectable ALK or NTRK expression...
April 20, 2018: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29682185/stat5-inhibition-induces-trail-dr4-dependent-apoptosis-in-peripheral-t-cell-lymphoma
#4
Haley M Simpson, Aki Furusawa, Kavitha Sadashivaiah, Curt I Civin, Arnob Banerjee
Peripheral T-cell lymphoma (PTCL) is a rare, aggressive, heterogeneous, Non-Hodgkin's lymphoma with poor prognosis and inadequate response to current therapies. Recent sequencing studies indicate a prevalence of activating mutations in the JAK/STAT signaling pathway. Oncogenic mutations in STAT5B, observed in approximately one third of cases of multiple different PTCL subtypes, correlate with inferior patient outcomes. Therefore, interest in the development of therapeutic strategies for targeting STAT5 in PTCL is warranted...
March 30, 2018: Oncotarget
https://www.readbyqxmd.com/read/29677173/what-does-this-mutation-mean-the-tools-and-pitfalls-of-variant-interpretation-in-lymphoid-malignancies
#5
REVIEW
Guillermin Yann, Lopez Jonathan, Chabane Kaddour, Hayette Sandrine, Bardel Claire, Salles Gilles, Sujobert Pierre, Huet Sarah
High throughput sequencing (HTS) is increasingly important in determining cancer diagnoses, with subsequent prognostic and therapeutic implications. The biology of cancer is becoming increasingly deciphered and it is clear that therapy needs to be individually tailored. Whilst translational research plays an important role in lymphoid malignancies, few guidelines exist to guide biologists and routine laboratories through this constantly evolving field. In this article, we review the challenges of interpreting HTS in lymphoid malignancies and provide a toolkit to interpret single nucleotide variants obtained from HTS...
April 20, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29675948/pattern-of-care-and-survival-of-anaplastic-lymphoma-kinase-rearranged-non-small-cell-lung-cancer-alk-nsclc-in-an-australian-metropolitan-tertiary-referral-centre-a-retrospective-cohort-analysis
#6
Malinda Itchins, Sarah A Hayes, Anthony J Gill, Wendy Cooper, Rachel O'Connell, Viive M Howell, Stephen J Clarke, Nick Pavlakis
AIM: To report on the pattern of care and survival of anaplastic lymphoma kinase rearranged non-small cell lung cancer (ALK+NSCLC) in a real-world retrospective cohort from an Australian tertiary referral center. METHODS: Individuals with a pathological diagnosis of ALK+NSCLC via immunohistochemistry and fluorescence in situ hybridization and a radiological diagnosis of stage IV disease were eligible. Patients were identified via the Pathology Department specimen database and electronic patient chart review...
April 19, 2018: Asia-Pacific Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29674676/comparative-high-resolution-transcriptome-sequencing-of-lymphoma-cell-lines-and-de-novo-lymphomas-reveals-cell-line-specific-pathway-dysregulation
#7
Leila Taher, Julia Beck, Wen Liu, Catrin Roolf, Jan T Soller, Barbara C Rütgen, Sabine E Hammer, Murali Chodisetti, Sina Sender, Katharina A Sterenczak, Georg Fuellen, Christian Junghanss, Bertram Brenig, Ingo Nolte, Ekkehard Schütz, Hugo Murua Escobar
In dogs as well as humans, lymphoma is one of the most common hematopoietic malignancies. Furthermore, due to its characteristics, canine lymphoma is recognized as a clinically relevant in vivo model to study the corresponding human disease. Immortalized cell lines are widely used as in vitro models to evaluate novel therapeutic agents and characterize their molecular mechanisms. However, it is known that long-term cultivation leads to clonal selection, genetic instability, and loss of the initial heterogenic character, limiting the usefulness of cell lines as preclinical models...
April 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29674644/aggressive-natural-killer-cell-leukemia-mutational-landscape-and-drug-profiling-highlight-jak-stat-signaling-as-therapeutic-target
#8
Olli Dufva, Matti Kankainen, Tiina Kelkka, Nodoka Sekiguchi, Shady Adnan Awad, Samuli Eldfors, Bhagwan Yadav, Heikki Kuusanmäki, Disha Malani, Emma I Andersson, Paavo Pietarinen, Leena Saikko, Panu E Kovanen, Teija Ojala, Dean A Lee, Thomas P Loughran, Hideyuki Nakazawa, Junji Suzumiya, Ritsuro Suzuki, Young Hyeh Ko, Won Seog Kim, Shih-Sung Chuang, Tero Aittokallio, Wing C Chan, Koichi Ohshima, Fumihiro Ishida, Satu Mustjoki
Aggressive natural killer-cell (NK-cell) leukemia (ANKL) is an extremely aggressive malignancy with dismal prognosis and lack of targeted therapies. Here, we elucidate the molecular pathogenesis of ANKL using a combination of genomic and drug sensitivity profiling. We study 14 ANKL patients using whole-exome sequencing (WES) and identify mutations in STAT3 (21%) and RAS-MAPK pathway genes (21%) as well as in DDX3X (29%) and epigenetic modifiers (50%). Additional alterations include JAK-STAT copy gains and tyrosine phosphatase mutations, which we show recurrent also in extranodal NK/T-cell lymphoma, nasal type (NKTCL) through integration of public genomic data...
April 19, 2018: Nature Communications
https://www.readbyqxmd.com/read/29674500/novel-gpr34-and-ccr6-mutation-and-distinct-genetic-profiles-in-malt-lymphomas-of-different-sites
#9
Sarah Moody, Joe Sneath Thompson, Shih-Sung Chuang, Hongxiang Liu, Markus Raderer, George Vassiliou, Iwona Wlodarska, Fangtian Wu, Sergio Cogliatti, Alistair Robson, Margaret Ashton-Key, Yingwen Bi, John Goodlad, Ming-Qing Du
MALT lymphoma originates from a background of diverse chronic inflammatory disorders at various anatomic sites. The genetics underlying its development, particularly in those associated with autoimmune disorders, is poorly characterised. By whole exome sequencing of 21 cases of MALT lymphomas of the salivary gland and thyroid, we have identified recurrent somatic mutations in 2 G-protein coupled receptors (GPR34 and CCR6) not previously reported in human malignancies, 3 genes (PIK3CD, TET2, TNFRSF14) not previously implicated in MALT lymphoma, and a further 2 genes (TBL1XR1, NOTCH1) recently described in MALT lymphoma...
April 19, 2018: Haematologica
https://www.readbyqxmd.com/read/29674443/recent-advances-in-the-treatment-of-peripheral-t-cell-lymphoma
#10
REVIEW
Kamel Laribi, Mustapha Alani, Catherine Truong, Alix Baugier de Materre
Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of clinically aggressive diseases associated with poor outcome. Despite progress in the last several years, resulting in a deeper understanding of the natural history and biology of PTCL based on molecular profiling and next-generation sequencing, there is a need for improvement in efficacy of chemotherapeutic regimens for newly diagnosed patients. Treatment in the front-line setting is most often cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP-like regimens, which are associated with a high failure rate and frequent relapses...
April 19, 2018: Oncologist
https://www.readbyqxmd.com/read/29673048/emerging-diagnostic-tests-for-vitreoretinal-lymphoma
#11
REVIEW
Abby C Dawson, Keryn A Williams, Binoy Appukuttan, Justine R Smith
Vitreoretinal lymphoma, which most commonly is diffuse large B cell non-Hodgkin in type, is a rare cancer with high morbidity and high mortality. Making a tissue diagnosis of vitreoretinal lymphoma is a major challenge for clinicians due to biological and technical factors. Yet, the delay in start of treatment may have vision- and life- threatening consequences, and there is considerable interest in the application of molecular assays to improve the accuracy of the diagnostic process: detection of a clonal immunoglobulin heavy chain rearrangements in lymphoma cells by polymerase chain reaction; measurement of vitreous or aqueous interleukin-10 protein levels in ocular fluids; and identification of mutations in the myeloid differentiation primary response gene 88 in tumour cells...
April 19, 2018: Clinical & Experimental Ophthalmology
https://www.readbyqxmd.com/read/29666117/novel-insights-into-the-pathogenesis-of-t-cell-lymphomas
#12
John S Van Arnam, Megan S Lim, Kojo S J Elenitoba-Johnson
T-cell lymphomas are a heterogeneous group of rare malignancies with overlapping clinical, immunologic and histologic features. Recent advances in our understanding of T-cell differentiation based on gene expression profiling, next-generation sequencing (NGS) and transgenic mouse modeling studies have better elucidated the pathogenetic mechanisms underlying the diverse biology of T-cell lymphomas. These studies show that while genetic alterations in epigenetic modifiers are implicated in all subtypes of T-cell lymphomas, specific subtypes demonstrate enrichment for particular recurrent alterations targeting specific genes...
April 17, 2018: Blood
https://www.readbyqxmd.com/read/29666005/unexpected-favorable-outcome-in-a-patient-with-high-grade-b-cell-lymphoma-with-abnormalities-of-myc-bcl6-and-bcl2-loci
#13
Thomas Adams, Deborah Fuchs, Patricia K Shadoan, Laurel Johnstone, Branden M Lau, Lee McGhan, Faiz Anwer, Hussam Al-Kateb
High grade B-cell lymphoma (HGBCL) by WHO 2016 classification requires rearrangements of MYC and BCL2 and/or BCL6, practically covering the so called "double-hit" or "triple hit" lymphomas. We report a case of HGBCL "triple-hit" lymphoma in a 64-year old female. Cytogenetic and fluorescence in situ hybridization (FISH) studies revealed complex karyotype including rearrangement of MYC to a novel, non-IG partner on chromosome 18, and rearrangement of BCL2, BCL6 and IGH as well as ins(3)(q21q27...
April 2018: Cancer Genetics
https://www.readbyqxmd.com/read/29665942/-research-progress-of-histone-modification-in-b-cell-lymphoma-pathogenesis-review
#14
Jiao Zhang, Yun Pan, Yan Li
It has been increasingly recognized that the pathogenesis of B-cell lymphoma closely relates to the epigenetic disregulations. Epigenetics is a subdiscipline, which means heritable changes in gene expressions without alterations in the DNA sequence, and the DNA methylation, histone modification and miRNA maily were involved. Histone modification is the most important epigenetic modification, the researches showed that the aberrant histone modification is the important pathogenesis in B-cell lymphoma, especially the aberrant histone methylation and acetylation...
April 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29665370/conservation-and-polymorphism-of-ebv-rpms1-gene-in-ebv-associated-tumors-and-healthy-individuals-from-endemic-and-non-endemic-nasopharyngeal-carcinoma-areas-in-china
#15
Shuo Wu, Wen Liu, Hong Li, Zhenzhen Zhao, Yang Yang, Hua Xiao, Yingying Song, Bing Luo
As a member of the BamHI-A rightward transcripts family of the Epstein-Barr virus (EBV), RPMS1 expression has been confirmed in all EBV-associated tumors. However, few studies have investigated the single-nucleotide polymorphisms (SNPs) of RPMS1, and only one SNP site (g155391a) has been reported to be associated with nasopharyngeal carcinoma occurrence. The objective of this study was to investigate the polymorphism of RPMS1 in EBV-associated tumors (gastric carcinoma, nasopharyngeal carcinoma, and lymphoma)...
April 14, 2018: Virus Research
https://www.readbyqxmd.com/read/29662631/overlap-at-the-molecular-and-immunohistochemical-levels-between-angioimmunoblastic-t-cell-lymphoma-and-a-subgroup-of-peripheral-t-cell-lymphomas-without-specific-morphological-features
#16
Rebeca Manso, Julia González-Rincón, Manuel Rodríguez-Justo, Giovanna Roncador, Sagrario Gómez, Margarita Sánchez-Beato, Miguel A Piris, Socorro M Rodríguez-Pinilla
The overlap of morphology and immunophenotype between angioimmunoblastic T-cell lymphoma (AITL) and other nodal peripheral T-cell lymphomas (n-PTCLs) is a matter of current interest whose clinical relevance and pathogenic background have not been fully established. We studied a series of 98 n-PTCL samples (comprising 57 AITL and 41 PTCL-NOS) with five TFH antibodies (CD10, BCL-6, PD-1, CXCL13, ICOS), looked for mutations in five of the genes most frequently mutated in AITL ( TET2 , DNMT3A, IDH2, RHOA and PLCG1 ) using the Next-Generation-Sequencing Ion Torrent platform, and measured the correlations of these characteristics with morphology and clinical features...
March 23, 2018: Oncotarget
https://www.readbyqxmd.com/read/29657294/rare-splice-variants-in-long-non-coding-rnas
#17
Rituparno Sen, Gero Doose, Peter F Stadler
Long non-coding RNAs (lncRNAs) form a substantial component of the transcriptome and are involved in a wide variety of regulatory mechanisms. Compared to protein-coding genes, they are often expressed at low levels and are restricted to a narrow range of cell types or developmental stages. As a consequence, the diversity of their isoforms is still far from being recorded and catalogued in its entirety, and the debate is ongoing about what fraction of non-coding RNAs truly conveys biological function rather than being "junk"...
July 5, 2017: Non-Coding RNA
https://www.readbyqxmd.com/read/29629950/a-survey-of-somatic-mutations-in-41-genes-in-a-cohort-of-t-cell-lymphomas-identifies-frequent-mutations-in-genes-involved-in-epigenetic-modification
#18
Sebastian Fernandez-Pol, Lisa Ma, Rohan P Joshi, Daniel A Arber
Here, we utilize a high throughput sequencing panel that covers several genes known to be recurrently mutated in certain T-cell lymphoma subtypes as well as genes frequently mutated in other hematolymphoid malignancies, including myeloid neoplasms. This panel was applied to formalin-fixed, paraffin-embedded tissue from 84 biopsies from 78 patients selected for this study. The biopsies included ones a with a diagnosis of T-cell lymphoma (n=79), including peripheral T-cell lymphoma not otherwise specified (PTCL-NOS; n=26) and angioimmunoblastic T-cell lymphoma (AITL; n=13), as well as 5 cases of atypical T-cell proliferations...
April 7, 2018: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/29629945/clonal-evolution-in-primary-diffuse-large-b-cell-lymphoma-of-the-central-nervous-system
#19
Julia Garcia-Reyero, Nerea Martinez Magunacelaya, Ainara Gonzalez Pereña, Sara Marcos Gonzalez, Nuria Teran-Villagra, Ainara Azueta, Ana Batlle, Sonia Gonzalez de Villambrosia, Jose Revert Arce, Santiago Montes-Moreno
Primary diffuse large B-cell lymphoma (DLBCL) of the central nervous system (CNS) is an aggressive subtype of DLBCL with characteristic clinicopathologic features. Relapse outside the CNS involving extranodal locations has been found in a fraction of cases (16%). Here we describe a case of DLBCL arising in the CNS that relapsed 18 months after the initial diagnosis in the testis and bilateral adrenal glands. Both tumors showed equivalent morphology, phenotype, cytogenetic features, and clonal relationship. Somatic mutation analysis by next generation sequencing demonstrated MYD88L265P mutation in both tumors and de novo CD79B Y196S mutation exclusive to the relapse...
April 7, 2018: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/29626238/primary-central-nervous-system-lymphoma-and-atypical-glioblastoma-differentiation-using-radiomics-approach
#20
Hie Bum Suh, Yoon Seong Choi, Sohi Bae, Sung Soo Ahn, Jong Hee Chang, Seok-Gu Kang, Eui Hyun Kim, Se Hoon Kim, Seung-Koo Lee
OBJECTIVES: To evaluate the diagnostic performance of magnetic resonance (MR) radiomics-based machine-learning algorithms in differentiating primary central nervous system lymphoma (PCNSL) from non-necrotic atypical glioblastoma (GBM). METHODS: Seventy-seven patients (54 individuals with PCNSL and 23 with non-necrotic atypical GBM), diagnosed from January 2009 to April 2017, were enrolled in this retrospective study. A total of 6,366 radiomics features, including shape, volume, first-order, texture, and wavelet-transformed features, were extracted from multi-parametric (post-contrast T1- and T2-weighted, and fluid attenuation inversion recovery images) and multiregional (enhanced and non-enhanced) tumour volumes...
April 6, 2018: European Radiology
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