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Genomic lymphoma

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https://www.readbyqxmd.com/read/29666292/human-immunodeficiency-virus-tat-protein-aids-v-region-somatic-hypermutation-in-human-b-cells
#1
Xiaohua Wang, Zhi Duan, Guojun Yu, Manxia Fan, Matthew D Scharff
Long-term survivors of human immunodeficiency virus (HIV) infection have been shown to have a greatly increased incidence of B cell lymphomas. This increased lymphomagenesis suggests some link between HIV infection and the destabilization of the host B cell genome, a phenomenon also suggested by the extraordinary high frequency of mutation, insertion, and deletion in the broadly neutralizing HIV antibodies. Since HIV does not infect B cells, the molecular mechanisms of this genomic instability remain to be fully defined...
April 17, 2018: MBio
https://www.readbyqxmd.com/read/29666115/genetics-of-diffuse-large-b-cell-lymphoma
#2
Laura Pasqualucci, Riccardo Dalla-Favera
Diffuse large B cell lymphoma (DLBCL), the most frequent subtype of lymphoid malignancy, remains a significant clinical challenge, as approximately 30% of patients are not cured. Over the past decade, remarkable progress has been made in the understanding of the pathogenesis of this disease, spurred by the implementation of powerful genomic technologies that enabled the definition of its genetic and epigenetic landscape. These studies have uncovered a multitude of genomic alterations that contribute to the initiation and maintenance of the tumor clone by disrupting biological functions known to be critical for the normal biology of its cells of origin, germinal center B cells...
April 17, 2018: Blood
https://www.readbyqxmd.com/read/29666114/chronic-lymphocytic-leukemia-and-mantle-cell-lymphoma-crossroads-of-genetic-and-microenvironment-interactions
#3
Xose S Puente, Pedro Jares, Elias Campo
Chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL) are two well defined entities that diverge in their basic pathogenic mechanisms and clinical evolution but they share epidemiological characteristics, cells of origin, molecular alterations, and clinical features that differ from other lymphoid neoplasms. CLL and MCL are classically considered indolent and aggressive neoplasms, respectively. However, the clinical evolution of both tumors is very heterogeneous, with subsets of patients having a stable disease for long time whereas others require immediate intervention...
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
#4
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/29657294/rare-splice-variants-in-long-non-coding-rnas
#5
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/29650799/pervasive-mutations-of-jak-stat-pathway-genes-in-classical-hodgkin-lymphoma
#6
Enrico Tiacci, Erik Ladewig, Gianluca Schiavoni, Alex Penson, Elisabetta Fortini, Valentina Pettirossi, Yuchun Wang, Ariele Rosseto, Alessandra Venanzi, Sofija Vlasevska, Roberta Pacini, Simonetta Piattoni, Alessia Tabarrini, Alessandra Pucciarini, Barbara Bigerna, Alessia Santi, Alessandro M Gianni, Simonetta Viviani, Antonello Cabras, Stefano Ascani, Barbara Crescenzi, Cristina Mecucci, Laura Pasqualucci, Raul Rabadan, Brunangelo Falini
Dissecting the pathogenesis of classical Hodgkin lymphoma (cHL), a common cancer in young adults, remains challenging due to the rarity of tumor cells in involved tissues (usually <5%). Here, we analyzed the coding genome of cHL by microdissecting tumor and normal cells from 34 patient biopsies, for a total of ~50,000 singly isolated lymphoma cells. We uncovered several recurrently mutated genes, namely STAT6 (32% of cases), GNA13 (24%), XPO1 (18%) and ITPKB (16%), and document the functional role of mutant STAT6 in sustaining tumor cell viability...
April 12, 2018: Blood
https://www.readbyqxmd.com/read/29649101/pathobiologic-roles-of-epstein-barr-virus-encoded-micrornas-in-human-lymphomas
#7
REVIEW
Mohsen Navari, Maryam Etebari, Mostafa Ibrahimi, Lorenzo Leoncini, Pier Paolo Piccaluga
Epstein-Barr virus (EBV) is a human γ-herpesvirus implicated in several human malignancies, including a wide range of lymphomas. Several molecules encoded by EBV in its latent state are believed to be related to EBV-induced lymphomagenesis, among which microRNAs-small RNAs with a posttranscriptional regulating role-are of great importance. The genome of EBV encodes 44 mature microRNAs belonging to two different classes, including BamHI-A rightward transcript ( BART ) and Bam HI fragment H rightward open reading frame 1 ( BHRF1 ), with different expression levels in different EBV latency types...
April 12, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29616865/single-agent-panobinostat-for-relapsed-refractory-diffuse-large-b-cell-lymphoma-clinical-outcome-and-correlation-with-genomic-data-a-phase-2-study-of-the-fondazione-italiana-linfomi
#8
Francesco Zaja, Flavia Salvi, Maura Rossi, Elena Sabattini, Andrea Evangelista, Giovannino Ciccone, Emanuele Angelucci, Gianluca Gaidano, Manuela Zanni, Marco Ladetto, Annalisa Chiappella, Umberto Vitolo, Pier Luigi Zinzani, Catello Califano, Alessandra Tucci, Caterina Patti, Stefano A Pileri, Valentina Lenti, Pier Paolo Piccaluga, Federica Cavallo, Stefano Volpetti, Giulia Perali, Sarit Assouline, Koren Kathleen Mann, Ryan Morin, Miguel Alcaide, Kevin Bushell, Renato Fanin, Alessandro Levis
We investigated panobinostat 40 mg three times weekly in 35 adult patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). Overall response rate and complete response were 17.1% and 11.4%, respectively. Median progression-free survival (PFS) and overall survival were 2.4 and 7.6 months, respectively. Calculated 12, 24 and 36 months PFS were 26%, 11% and 11%, respectively. Four patients who achieved a sustained CR, continued receiving panobinostat for an overall period of 44, 48, 50, 62 months...
April 4, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29616191/ataxia-telangiectasia-mutated-kinase-in-the-control-of-oxidative-stress-mitochondria-and-autophagy-in-cancer-a-maestro-with-a-large-orchestra
#9
REVIEW
Venturina Stagni, Claudia Cirotti, Daniela Barilà
Ataxia-telangiectasia mutated kinase (ATM) plays a central role in the DNA damage response (DDR) and mutations in its gene lead to the development of a rare autosomic genetic disorder, ataxia telangiectasia (A-T) characterized by neurodegeneration, premature aging, defects in the immune response, and higher incidence of lymphoma development. The ability of ATM to control genome stability several pointed to ATM as tumor suppressor gene. Growing evidence clearly support a significant role of ATM, in addition to its master ability to control the DDR, as principle modulator of oxidative stress response and mitochondrial homeostasis, as well as in the regulation of autophagy, hypoxia, and cancer stem cell survival...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29616088/retrospective-screening-of-microarray-data-to-identify-candidate-ifn-inducible-genes-in-a-htlv-1-transformed-model
#10
Alaa Refaat, Mohamed Owis, Sherif Abdelhamed, Ikuo Saiki, Hiroaki Sakurai
HuT-102 cells are considered one of the most representable human T-lymphotropic virus 1 (HTLV-1)-infected cell lines for studying adult T-cell lymphoma (ATL). In our previous studies, genome-wide screening was performed using the GeneChip system with Human Genome Array U133 Plus 2.0 for transforming growth factor-β-activated kinase 1 (TAK1)-, interferon regulatory factor 3 (IRF3)- and IRF4-regulated genes to demonstrate the effects of interferon-inducible genes in HuT-102 cells. Our previous findings demonstrated that TAK1 induced interferon inducible genes via an IRF3-dependent pathway and that IRF4 has a counteracting effect...
April 2018: Oncology Letters
https://www.readbyqxmd.com/read/29615404/the-tumor-suppressive-tgf-%C3%AE-smad1-s1pr2-signaling-axis-is-recurrently-inactivated-in-diffuse-large-b-cell-lymphoma
#11
Anna Stelling, Hind Hashwah, Katrin Bertram, Markus G Manz, Alexandar Tzankov, Anne Müller
The sphingosine-1-phosphate receptor S1PR2 and its downstream signaling pathway is commonly silenced in diffuse large B-cell lymphoma (DLBCL), either by mutational inactivation or through negative regulation by the oncogenic transcription factor FOXP1. In this study, we have examined the upstream regulators of S1PR2 expression and have newly identified the TGF-β/TGF-βR2/SMAD1 axis as critically involved in S1PR2 transcriptional activation. Phosphorylated SMAD1 directly binds to regulatory elements in the S1PR2 locus as assessed by chromatin immunoprecipitation, and the CRISPR-mediated genomic editing of S1PR2 , SMAD1 or TGFBR2 in DLBCL cell lines renders cells unresponsive to TGF-β-induced apoptosis...
April 3, 2018: Blood
https://www.readbyqxmd.com/read/29599530/excessive-activated-t-cell-proliferation-after-anti-cd19-car-t-cell-therapy
#12
Wen-Ying Zhang, Yang Liu, Yao Wang, Jing Nie, Ye-Lei Guo, Chun-Meng Wang, Han-Ren Dai, Qing-Ming Yang, Zhi-Qiang Wu, Wei-Dong Han
Excessive activated T-cell proliferation was observed in vivo in one patient after an anti-CD19-chimeric antigen receptor (CAR) T-cell infusion. The patient, who had chemotherapy refractory and CD19+ diffuse large B-cell lymphoma (DLBCL), received an anti-CD19 CAR T-cell infusion following conditioning chemotherapy (fludarabine/cyclophosphamide). The lymphocyte count in the peripheral blood (PB) increased to 77 × 109 /L on day 13 post infusion, and the proportion of CD8+ actived T cells was 93.06% of the lymphocytes...
March 29, 2018: Gene Therapy
https://www.readbyqxmd.com/read/29599410/clinical-utility-of-cell-free-dna-for-the-detection-of-alk-fusions-and-genomic-mechanisms-of-alk-inhibitor-resistance-in-non-small-cell-lung-cancer
#13
Caroline E McCoach, Collin M Blakely, Kimberly C Banks, Benjamin Levy, Ben M Chue, Victoria M Raymond, Anh Le, Christine E Lee, Joseph Diaz, Saiama N Waqar, W Thomas Purcell, Dara L Aisner, Kurtis D Davies, Richard B Lanman, Alice T Shaw, Robert C Doebele
PURPOSE: Patients with advanced non-small cell lung cancer (NSCLC) whose tumors harbor anaplastic lymphoma kinase ALK gene fusions benefit from treatment with ALK inhibitors (ALKi). Analysis of cell-free circulating tumor DNA (cfDNA) may provide a non-invasive way to identify ALK fusions and actionable resistance mechanisms without biopsy. EXPERIMENTAL DESIGN: The Guardant360 (G360) de-identified database of NSCLC cases was queried to identify 88 consecutive patients with 96 plasma-detected ALK fusions...
March 29, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29587466/chromosomal-instability-in-hodgkin-lymphoma-an-in-depth-review-and-perspectives
#14
REVIEW
Corina Cuceu, William M Hempel, Laure Sabatier, Jacques Bosq, Patrice Carde, Radhia M'kacher
The study of Hodgkin lymphoma (HL), with its unique microenvironment and long-term follow-up, has provided exceptional insights into several areas of tumor biology. Findings in HL have not only improved our understanding of human carcinogenesis, but have also pioneered its translation into the clinics. HL is a successful paradigm of modern treatment strategies. Nonetheless, approximately 15-20% of patients with advanced stage HL still die following relapse or progressive disease and a similar proportion of patients are over-treated, leading to treatment-related late sequelae, including solid tumors and organ dysfunction...
March 26, 2018: Cancers
https://www.readbyqxmd.com/read/29581848/aberrant-expression-of-nkl-homeobox-gene-hlx-in-hodgkin-lymphoma
#15
Stefan Nagel, Claudia Pommerenke, Corinna Meyer, Maren Kaufmann, Roderick A F MacLeod, Hans G Drexler
NKL homeobox genes are basic regulators of cell and tissue differentiation, many acting as oncogenes in T-cell leukemia. Recently, we described an hematopoietic NKL-code comprising six particular NKL homeobox genes expressed in hematopoietic stem cells and lymphoid progenitors, unmasking their physiological roles in the development of these cell types. Hodgkin lymphoma (HL) is a B-cell malignancy showing aberrant activity of several developmental genes resulting in disturbed B-cell differentiation. To examine potential concordances in abnormal lymphoid differentiation of T- and B-cell malignancies we analyzed the expression of the hematopoietic NKL-code associated genes in HL, comprising HHEX, HLX, MSX1, NKX2-3, NKX3-1 and NKX6-3...
March 6, 2018: Oncotarget
https://www.readbyqxmd.com/read/29568910/downregulation-of-mir-374b-5p-promotes-chemotherapeutic-resistance-in-pancreatic-cancer-by-upregulating-multiple-anti-apoptotic-proteins
#16
Di Sun, Xu Wang, Guoqing Sui, Si Chen, Miao Yu, Ping Zhang
Resistance to first-line chemotherapeutic drugs such as gemcitabine contributes to the poor prognosis of patients with pancreatic cancer. MicroRNAs (miRNA) regulate chemoresistance in pancreatic cancer. By analyzing the miRNA sequencing dataset of pancreatic cancer from The Cancer Genome Atlas, it was demonstrated that miR-374b-5p expression was dramatically reduced in pancreatic cancer tissues compared with adjacent normal tissues, as well as decreased in chemoresistant compared with chemosensitive pancreatic carcinoma tissues...
March 14, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29568095/genomic-profiling-reveals-spatial-intra-tumor-heterogeneity-in-follicular-lymphoma
#17
Shamzah Araf, Jun Wang, Koorosh Korfi, Celine Pangault, Eleni Kotsiou, Ana Rio-Machin, Tahrima Rahim, James Heward, Andrew Clear, Sameena Iqbal, Jeff K Davies, Peter Johnson, Maria Calaminici, Silvia Montoto, Rebecca Auer, Claude Chelala, John G Gribben, Trevor A Graham, Thierry Fest, Jude Fitzgibbon, Jessica Okosun
No abstract text is available yet for this article.
February 8, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29567880/myeloid-cell-leukemia-1-protein-expression-and-myeloid-cell-leukemia-1-gene-amplification-in-non-small-cell-lung-cancer
#18
Tony El Jabbour, Siddhartha Dilip Dalvi, Sungeun Kim, Christine Sheehan, Jeffrey S Ross
Background: Myeloid cell leukemia-1 (Mcl-1) is a member of the B-cell lymphoma 2 family known to play a significant role in the regulation of apoptosis. Mcl-1 expression has been studied in nonsmall cell lung cancer (NSCLC) cell lines but has not been previously evaluated as a prognostic factor in clinical samples. Materials and Methods: Formalin-fixed, paraffin-embedded sections from 119 NSCLC, including 33 squamous cell carcinomas (SCC), 55 adenocarcinomas (AC), and 31 either pure adenocarcinoma in situ (AIS) or AC with lepidic features were immunostained by an automated method with rabbit polyclonal Mcl-1...
January 2018: Indian Journal of Pathology & Microbiology
https://www.readbyqxmd.com/read/29566098/pdz-domain-binding-motif-of-tax-sustains-t-cell-proliferation-in-htlv-1-infected-humanized-mice
#19
Eléonore Pérès, Juliana Blin, Emiliano P Ricci, Maria Artesi, Vincent Hahaut, Anne Van den Broeke, Antoine Corbin, Louis Gazzolo, Lee Ratner, Pierre Jalinot, Madeleine Duc Dodon
Human T-cell leukemia virus type 1 (HTLV-1) is the etiological agent of adult T-cell leukemia/lymphoma (ATLL), an aggressive malignant proliferation of activated CD4+ T lymphocytes. The viral Tax oncoprotein is critically involved in both HTLV-1-replication and T-cell proliferation, a prerequisite to the development of ATLL. In this study, we investigated the in vivo contribution of the Tax PDZ domain-binding motif (PBM) to the lymphoproliferative process. To that aim, we examined T-cell proliferation in humanized mice (hu-mice) carrying a human hemato-lymphoid system infected with either a wild type (WT) or a Tax PBM-deleted (ΔPBM) provirus...
March 22, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29564828/genes-proteins-and-biological-pathways-preventing-chromothripsis
#20
Martin Poot
The highly complex structural genome variations chromothripsis, chromoanasynthesis, and chromoplexy are subsumed under the term chromoanagenesis, which means chromosome rebirth. Precipitated by numerous DNA double-strand breaks, they differ in number of and distances between breakpoints, associated copy number variations, order and orientation of segments, and flanking sequences at joining points. Results from patients with the autosomal dominant cancer susceptibility disorder Li-Fraumeni syndrome implicated somatic TP53 mutations in chromothripsis...
2018: Methods in Molecular Biology
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