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Article ; Online: Methylation-directed regulatory networks determine enhancing and silencing of mutation disease driver genes and explain inter-patient expression variation.

Edrei, Yifat / Levy, Revital / Kaye, Daniel / Marom, Anat / Radlwimmer, Bernhard / Hellman, Asaf

2023 Volume 24, Issue 1, Page(s) 264

Abstract: Background: Common diseases manifest differentially between patients, but the genetic origin of this variation remains unclear. To explore possible involvement of gene transcriptional-variation, we produce a DNA methylation-oriented, driver-gene-wide ... ...

Abstract	Background: Common diseases manifest differentially between patients, but the genetic origin of this variation remains unclear. To explore possible involvement of gene transcriptional-variation, we produce a DNA methylation-oriented, driver-gene-wide dataset of regulatory elements in human glioblastomas and study their effect on inter-patient gene expression variation. Results: In 175 of 177 analyzed gene regulatory domains, transcriptional enhancers and silencers are intermixed. Under experimental conditions, DNA methylation induces enhancers to alter their enhancing effects or convert into silencers, while silencers are affected inversely. High-resolution mapping of the association between DNA methylation and gene expression in intact genomes reveals methylation-related regulatory units (average size = 915.1 base-pairs). Upon increased methylation of these units, their target-genes either increased or decreased in expression. Gene-enhancing and silencing units constitute cis-regulatory networks of genes. Mathematical modeling of the networks highlights indicative methylation sites, which signified the effect of key regulatory units, and add up to make the overall transcriptional effect of the network. Methylation variation in these sites effectively describe inter-patient expression variation and, compared with DNA sequence-alterations, appears as a major contributor of gene-expression variation among glioblastoma patients. Conclusions: We describe complex cis-regulatory networks, which determine gene expression by summing the effects of positive and negative transcriptional inputs. In these networks, DNA methylation induces both enhancing and silencing effects, depending on the context. The revealed mechanism sheds light on the regulatory role of DNA methylation, explains inter-individual gene-expression variation, and opens the way for monitoring the driving forces behind deferential courses of cancer and other diseases.
MeSH term(s)	Humans ; DNA Methylation ; Regulatory Sequences, Nucleic Acid ; Gene Expression Regulation ; Mutation
Language	English
Publishing date	2023-11-28
Publishing country	England
Document type	Journal Article
ZDB-ID	2040529-7
ISSN	1474-760X ; 1474-760X
ISSN (online)	1474-760X
ISSN	1474-760X
DOI	10.1186/s13059-023-03094-6
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Article ; Online: Branched-chain amino acid transaminase 1 regulates glioblastoma cell plasticity and contributes to immunosuppression.

Boskovic, Pavle / Wilke, Nathalie / Man, Ka-Hou / Lichter, Peter / Francois, Liliana / Radlwimmer, Bernhard

Neuro-oncology

2023 Volume 26, Issue 2, Page(s) 251–265

Abstract: Background: Glioblastoma is the most common malignant brain tumor in adults. Cellular plasticity and the poorly differentiated features result in a fast relapse of the tumors following treatment. Moreover, the immunosuppressive microenvironment proved ... ...

Abstract	Background: Glioblastoma is the most common malignant brain tumor in adults. Cellular plasticity and the poorly differentiated features result in a fast relapse of the tumors following treatment. Moreover, the immunosuppressive microenvironment proved to be a major obstacle to immunotherapeutic approaches. Branched-chain amino acid transaminase 1 (BCAT1) was shown to drive the growth of glioblastoma and other cancers;however, its oncogenic mechanism remains poorly understood. Methods: Using human tumor data, cell line models and orthotopic immuno-competent and -deficient mouse models, we investigated the phenotypic and mechanistic effects of BCAT1 on glioblastoma cell state and immunomodulation. Results: Here, we show that BCAT1 is crucial for maintaining the poorly differentiated state of glioblastoma cells and that its low expression correlates with a more differentiated glioblastoma phenotype. Furthermore, orthotopic tumor injection into immunocompetent mice demonstrated that the brain microenvironment is sufficient to induce differentiation of Bcat1-KO tumors in vivo. We link the transition to a differentiated cell state to the increased activity of ten-eleven translocation demethylases and the hypomethylation and activation of neuronal differentiation genes. In addition, the knockout of Bcat1 attenuated immunosuppression, allowing for an extensive infiltration of CD8+ cytotoxic T-cells and complete abrogation of tumor growth. Further analysis in immunodeficient mice revealed that both tumor cell differentiation and immunomodulation following BCAT1-KO contribute to the long-term suppression of tumor growth. Conclusions: Our study unveils BCAT1's pivotal role in promoting glioblastoma growth by inhibiting tumor cell differentiation and sustaining an immunosuppressive milieu. These findings offer a novel therapeutic avenue for targeting glioblastoma through the inhibition of BCAT1.
MeSH term(s)	Humans ; Mice ; Animals ; Glioblastoma ; Cell Plasticity ; Cell Proliferation ; Immunosuppression Therapy ; Transaminases/genetics ; Transaminases/metabolism ; Amino Acids, Branched-Chain/metabolism ; Tumor Microenvironment
Chemical Substances	Transaminases (EC 2.6.1.-) ; Amino Acids, Branched-Chain ; BCAT1 protein, human (EC 2.6.1.)
Language	English
Publishing date	2023-09-28
Publishing country	England
Document type	Journal Article
ZDB-ID	2028601-6
ISSN	1523-5866 ; 1522-8517
ISSN (online)	1523-5866
ISSN	1522-8517
DOI	10.1093/neuonc/noad190
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Article ; Online: BCAT1 redox function maintains mitotic fidelity.

Francois, Liliana / Boskovic, Pavle / Knerr, Julian / He, Wei / Sigismondo, Gianluca / Schwan, Carsten / More, Tushar H / Schlotter, Magdalena / Conway, Myra E / Krijgsveld, Jeroen / Hiller, Karsten / Grosse, Robert / Lichter, Peter / Radlwimmer, Bernhard

Cell reports

2023 Volume 42, Issue 3, Page(s) 112217

Language	English
Publishing date	2023-03-01
Publishing country	United States
Document type	Published Erratum
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2023.112217
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Article ; Online: BCAT1 redox function maintains mitotic fidelity.

Cell reports

2022 Volume 41, Issue 3, Page(s) 111524

Abstract: The metabolic enzyme branched-chain amino acid transaminase 1 (BCAT1) drives cell proliferation in aggressive cancers such as glioblastoma. Here, we show that BCAT1 localizes to mitotic structures and has a non-metabolic function as a mitotic regulator. ... ...

Abstract	The metabolic enzyme branched-chain amino acid transaminase 1 (BCAT1) drives cell proliferation in aggressive cancers such as glioblastoma. Here, we show that BCAT1 localizes to mitotic structures and has a non-metabolic function as a mitotic regulator. Furthermore, BCAT1 is required for chromosome segregation in cancer and induced pluripotent stem cells and tumor growth in human cerebral organoid and mouse syngraft models. Applying gene knockout and rescue strategies, we show that the BCAT1 CXXC redox motif is crucial for controlling cysteine sulfenylation specifically in mitotic cells, promoting Aurora kinase B localization to centromeres, and securing accurate chromosome segregation. These findings offer an explanation for the well-established role of BCAT1 in promoting cancer cell proliferation. In summary, our data establish BCAT1 as a component of the mitotic apparatus that safeguards mitotic fidelity through a moonlighting redox functionality.
MeSH term(s)	Animals ; Humans ; Mice ; Amino Acids, Branched-Chain ; Aurora Kinase B ; Cysteine ; Disease Models, Animal ; Oxidation-Reduction ; Transaminases
Chemical Substances	Amino Acids, Branched-Chain ; Aurora Kinase B (EC 2.7.11.1) ; BCAT1 protein, human (EC 2.6.1.) ; Cysteine (K848JZ4886) ; Transaminases (EC 2.6.1.-) ; Bcat1 protein, mouse (EC 2.6.1.)
Language	English
Publishing date	2022-11-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2022.111524
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Article ; Online: Rapid, adaptable and sensitive Cas13-based COVID-19 diagnostics using ADESSO.

Casati, Beatrice / Verdi, Joseph Peter / Hempelmann, Alexander / Kittel, Maximilian / Klaebisch, Andrea Gutierrez / Meister, Bianca / Welker, Sybille / Asthana, Sonal / Di Giorgio, Salvatore / Boskovic, Pavle / Man, Ka Hou / Schopp, Meike / Ginno, Paul Adrian / Radlwimmer, Bernhard / Stebbins, Charles Erec / Miethke, Thomas / Papavasiliou, Fotini Nina / Pecori, Riccardo

Nature communications

2022 Volume 13, Issue 1, Page(s) 3308

Abstract: During the ongoing COVID-19 pandemic, PCR testing and antigen tests have proven critical for helping to stem the spread of its causative agent, SARS-CoV-2. However, these methods suffer from either general applicability and/or sensitivity. Moreover, the ... ...

Abstract	During the ongoing COVID-19 pandemic, PCR testing and antigen tests have proven critical for helping to stem the spread of its causative agent, SARS-CoV-2. However, these methods suffer from either general applicability and/or sensitivity. Moreover, the emergence of variant strains creates the need for flexibility to correctly and efficiently diagnose the presence of substrains. To address these needs we developed the diagnostic test ADESSO (Accurate Detection of Evolving SARS-CoV-2 through SHERLOCK (Specific High Sensitivity Enzymatic Reporter UnLOCKing) Optimization) which employs Cas13 to diagnose patients in 1 h without sophisticated equipment. Using an extensive panel of clinical samples, we demonstrate that ADESSO correctly identifies infected individuals at a sensitivity and specificity comparable to RT-qPCR on extracted RNA and higher than antigen tests for unextracted samples. Altogether, ADESSO is a fast, sensitive and cheap method that can be applied in a point of care setting to diagnose COVID-19 and can be quickly adjusted to detect new variants.
MeSH term(s)	COVID-19/diagnosis ; COVID-19 Testing ; Humans ; Pandemics ; RNA, Viral/analysis ; RNA, Viral/genetics ; SARS-CoV-2 ; Sensitivity and Specificity
Chemical Substances	RNA, Viral
Language	English
Publishing date	2022-06-08
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-022-30862-y
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Article ; Online: Leucine and branched-chain amino acid metabolism contribute to the growth of bone sarcomas by regulating AMPK and mTORC1 signaling.

Martin, Shailer B / Reiche, William S / Fifelski, Nicholas A / Schultz, Alexander J / Stanford, Spencer J / Martin, Alexander A / Nack, Danielle L / Radlwimmer, Bernhard / Boyer, Michael P / Ananieva, Elitsa A

The Biochemical journal

2020 Volume 477, Issue 9, Page(s) 1579–1599

Abstract: Osteosarcoma and chondrosarcoma are sarcomas of the bone and the cartilage that are primarily treated by surgical intervention combined with high toxicity chemotherapy. In search of alternative metabolic approaches to address the challenges in treating ... ...

Abstract	Osteosarcoma and chondrosarcoma are sarcomas of the bone and the cartilage that are primarily treated by surgical intervention combined with high toxicity chemotherapy. In search of alternative metabolic approaches to address the challenges in treating bone sarcomas, we assessed the growth dependence of these cancers on leucine, one of the branched-chain amino acids (BCAAs), and BCAA metabolism. Tumor biopsies from bone sarcoma patients revealed differential expression of BCAA metabolic enzymes. The cytosolic branched-chain aminotransferase (BCATc) that is commonly overexpressed in cancer cells, was down-regulated in chondrosarcoma (SW1353) in contrast with osteosarcoma (143B) cells that expressed both BCATc and its mitochondrial isoform BCATm. Treating SW1353 cells with gabapentin, a selective inhibitor of BCATc, further revealed that these cells failed to respond to gabapentin. Application of the structural analog of leucine, N-acetyl-leucine amide (NALA) to disrupt leucine uptake, indicated that all bone sarcoma cells used leucine to support their energy metabolism and biosynthetic demands. This was evident from the increased activity of the energy sensor AMP-activated protein kinase (AMPK), down-regulation of complex 1 of the mammalian target of rapamycin (mTORC1), and reduced cell viability in response to NALA. The observed changes were most profound in the 143B cells, which appeared highly dependent on cytosolic and mitochondrial BCAA metabolism. This study thus demonstrates that bone sarcomas rely on leucine and BCAA metabolism for energy and growth; however, the differential expression of BCAA enzymes and the presence of other carbon sources may dictate how efficiently these cancer cells take advantage of BCAA metabolism.
MeSH term(s)	AMP-Activated Protein Kinases/metabolism ; Amino Acids, Branched-Chain/metabolism ; Bone Neoplasms/metabolism ; Cell Line, Tumor ; Chondrosarcoma/metabolism ; Cytosol/metabolism ; Energy Metabolism ; Humans ; Leucine/metabolism ; Mechanistic Target of Rapamycin Complex 1/metabolism ; Mitochondria/metabolism ; Osteosarcoma/metabolism ; Signal Transduction ; TOR Serine-Threonine Kinases/metabolism ; Transaminases/metabolism
Chemical Substances	Amino Acids, Branched-Chain ; Transaminases (EC 2.6.1.-) ; branched-chain-amino-acid transaminase (EC 2.6.1.42) ; TOR Serine-Threonine Kinases (EC 2.7.1.1) ; Mechanistic Target of Rapamycin Complex 1 (EC 2.7.11.1) ; AMP-Activated Protein Kinases (EC 2.7.11.31) ; Leucine (GMW67QNF9C)
Language	English
Publishing date	2020-04-15
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2969-5
ISSN	1470-8728 ; 0006-2936 ; 0306-3275 ; 0264-6021
ISSN (online)	1470-8728
ISSN	0006-2936 ; 0306-3275 ; 0264-6021
DOI	10.1042/BCJ20190754
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Article ; Online: Pilocytic astrocytoma demethylation and transcriptional landscapes link bZIP transcription factors to immune response.

Aichmüller, Christian F / Iskar, Murat / Jones, David T W / Korshunov, Andrey / Radlwimmer, Bernhard / Kool, Marcel / Ernst, Aurelie / Pfister, Stefan M / Lichter, Peter / Zapatka, Marc

Neuro-oncology

2020 Volume 22, Issue 9, Page(s) 1327–1338

Abstract: Background: Pilocytic astrocytoma (PA) is the most common pediatric brain tumor. While genome and transcriptome landscapes are well studied, data of the complete methylome, tumor cell composition, and immune infiltration are scarce.: Methods: We ... ...

Abstract	Background: Pilocytic astrocytoma (PA) is the most common pediatric brain tumor. While genome and transcriptome landscapes are well studied, data of the complete methylome, tumor cell composition, and immune infiltration are scarce. Methods: We generated whole genome bisulfite sequence (WGBS) data of 9 PAs and 16 control samples and integrated available 154 PA and 57 control methylation array data. RNA sequence data of 49 PAs and 11 control samples as well as gene expression arrays of 248 PAs and 28 controls were used to assess transcriptional activity. Results: DNA-methylation patterns of partially methylated domains suggested high stability of the methylomes during tumorigenesis. Comparing tumor and control tissues of infra- and supratentorial location using methylation arrays revealed a site specific pattern. Analysis of WGBS data revealed 9381 significantly differentially methylated regions (DMRs) in PA versus control tissue. Enhancers and transcription factor (TF) motifs of five distinct TF families were found to be enriched in DMRs. Methylation together with gene expression data-based in silico tissue deconvolution analysis indicated a striking variation in the immune cell infiltration in PA. A TF network analysis showed a regulatory relation between basic leucine zipper (bZIP) transcription factors and genes involved in immune-related processes. Conclusion: We provide evidence for a link of focal methylation differences and differential gene expression to immune infiltration.
MeSH term(s)	Astrocytoma/genetics ; Basic-Leucine Zipper Transcription Factors ; Child ; DNA Methylation ; Demethylation ; Humans ; Immunity
Chemical Substances	Basic-Leucine Zipper Transcription Factors
Language	English
Publishing date	2020-02-13
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2028601-6
ISSN	1523-5866 ; 1522-8517
ISSN (online)	1523-5866
ISSN	1522-8517
DOI	10.1093/neuonc/noaa035
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Article: A Set of Cell Lines Derived from a Genetic Murine Glioblastoma Model Recapitulates Molecular and Morphological Characteristics of Human Tumors.

Costa, Barbara / Fletcher, Michael N C / Boskovic, Pavle / Ivanova, Ekaterina L / Eisemann, Tanja / Lohr, Sabrina / Bunse, Lukas / Löwer, Martin / Burchard, Stefanie / Korshunov, Andrey / Coltella, Nadia / Cusimano, Melania / Naldini, Luigi / Liu, Hai-Kun / Platten, Michael / Radlwimmer, Bernhard / Angel, Peter / Peterziel, Heike

Cancers

2021 Volume 13, Issue 2

Abstract: Glioblastomas (GBM) are the most aggressive tumors affecting the central nervous system in adults, causing death within, on average, 15 months after diagnosis. Immunocompetent in-vivo models that closely mirror human GBM are urgently needed for ... ...

Abstract	Glioblastomas (GBM) are the most aggressive tumors affecting the central nervous system in adults, causing death within, on average, 15 months after diagnosis. Immunocompetent in-vivo models that closely mirror human GBM are urgently needed for deciphering glioma biology and for the development of effective treatment options. The murine GBM cell lines currently available for engraftment in immunocompetent mice are not only exiguous but also inadequate in representing prominent characteristics of human GBM such as infiltrative behavior, necrotic areas, and pronounced tumor heterogeneity. Therefore, we generated a set of glioblastoma cell lines by repeated in vivo passaging of cells isolated from a neural stem cell-specific
Language	English
Publishing date	2021-01-10
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers13020230
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Article ; Online: P

Lüddecke, Jan / Francois, Liliana / Spät, Philipp / Watzer, Björn / Chilczuk, Tomasz / Poschet, Gernot / Hell, Rüdiger / Radlwimmer, Bernhard / Forchhammer, Karl

Scientific reports

2017 Volume 7, Issue 1, Page(s) 1437

Abstract: The citric acid cycle intermediate 2-oxoglutarate (2-OG, a.k.a. alpha-ketoglutarate) links the carbon and nitrogen metabolic pathways and can provide information on the metabolic status of cells. In recent years, it has become exceedingly clear that 2-OG ...

Abstract	The citric acid cycle intermediate 2-oxoglutarate (2-OG, a.k.a. alpha-ketoglutarate) links the carbon and nitrogen metabolic pathways and can provide information on the metabolic status of cells. In recent years, it has become exceedingly clear that 2-OG also acts as a master regulator of diverse biologic processes in all domains of life. Consequently, there is a great demand for time-resolved data on 2-OG fluctuations that can't be adequately addressed using established methods like mass spectrometry-based metabolomics analysis. Therefore, we set out to develop a novel intramolecular 2-OG FRET sensor based on the signal transduction protein P
MeSH term(s)	Biosensing Techniques ; Cell Line, Tumor ; Chlamydomonas reinhardtii/genetics ; Chlamydomonas reinhardtii/metabolism ; Citric Acid Cycle/genetics ; Cloning, Molecular ; Epithelial Cells/cytology ; Epithelial Cells/metabolism ; Escherichia coli/genetics ; Escherichia coli/metabolism ; Escherichia coli K12/genetics ; Escherichia coli K12/metabolism ; Fluorescence Resonance Energy Transfer ; Gene Expression ; Gene Expression Regulation, Bacterial ; Genetic Vectors/chemistry ; Genetic Vectors/metabolism ; Glutamate Synthase/genetics ; Glutamate Synthase/metabolism ; Humans ; Ketoglutaric Acids/analysis ; Ketoglutaric Acids/metabolism ; Neuroglia/cytology ; Neuroglia/metabolism ; PII Nitrogen Regulatory Proteins/genetics ; PII Nitrogen Regulatory Proteins/metabolism ; Protein Engineering ; Recombinant Proteins/genetics ; Recombinant Proteins/metabolism ; Signal Transduction ; Synechococcus/genetics ; Synechococcus/metabolism
Chemical Substances	Ketoglutaric Acids ; PII Nitrogen Regulatory Proteins ; Recombinant Proteins ; Glutamate Synthase (EC 1.4.1.13)
Language	English
Publishing date	2017-05-03
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-017-01440-w
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Article ; Online: Focal structural variants revealed by whole genome sequencing disrupt the histone demethylase KDM4C in B-cell lymphomas.

Lopez, Cristina / Schleussner, Nikolai / Bernhart, Stephan H / Kleinheinz, Kortine / Sungalee, Stephanie / Sczakiel, Henrike L / Kretzmer, Helene / Toprak, Umut H / Glaser, Selina / Wagener, Rabea / Ammerpohl, Ole / Bens, Susanne / Giefing, Maciej / Sanchez, Juan C Gonzalez / Apic, Gordana / Hubschmann, Daniel / Janz, Martin / Kreuz, Markus / Mottok, Anja /

Muller, Judith M / Seufert, Julian / Hoffmann, Steve / Korbel, Jan O / Russell, Robert B / Schule, Roland / Trumper, Lorenz / Klapper, Wolfram / Radlwimmer, Bernhard / Lichter, Peter / Kuppers, Ralf / Schlesner, Matthias / Mathas, Stephan / Siebert, Reiner

Haematologica

2023 Volume 108, Issue 2, Page(s) 543–554

Abstract: Histone methylation-modifiers, such as EZH2 and KMT2D, are recurrently altered in B-cell lymphomas. To comprehensively describe the landscape of alterations affecting genes encoding histone methylation-modifiers in lymphomagenesis we investigated whole ... ...

Abstract	Histone methylation-modifiers, such as EZH2 and KMT2D, are recurrently altered in B-cell lymphomas. To comprehensively describe the landscape of alterations affecting genes encoding histone methylation-modifiers in lymphomagenesis we investigated whole genome and transcriptome data of 186 mature B-cell lymphomas sequenced in the ICGC MMML-Seq project. Besides confirming common alterations of KMT2D (47% of cases), EZH2 (17%), SETD1B (5%), PRDM9 (4%), KMT2C (4%), and SETD2 (4%), also identified by prior exome or RNA-sequencing studies, we here found recurrent alterations to KDM4C in chromosome 9p24, encoding a histone demethylase. Focal structural variation was the main mechanism of KDM4C alterations, and was independent from 9p24 amplification. We also identified KDM4C alterations in lymphoma cell lines including a focal homozygous deletion in a classical Hodgkin lymphoma cell line. By integrating RNA-sequencing and genome sequencing data we predict that KDM4C structural variants result in loss-offunction. By functional reconstitution studies in cell lines, we provide evidence that KDM4C can act as a tumor suppressor. Thus, we show that identification of structural variants in whole genome sequencing data adds to the comprehensive description of the mutational landscape of lymphomas and, moreover, establish KDM4C as a putative tumor suppressive gene recurrently altered in subsets of B-cell derived lymphomas.
MeSH term(s)	Humans ; Histones/metabolism ; Histone Demethylases/genetics ; Homozygote ; Sequence Deletion ; Lymphoma/genetics ; Lymphoma, B-Cell/genetics ; Whole Genome Sequencing ; RNA ; Jumonji Domain-Containing Histone Demethylases/genetics ; Jumonji Domain-Containing Histone Demethylases/chemistry ; Jumonji Domain-Containing Histone Demethylases/metabolism ; Histone-Lysine N-Methyltransferase/genetics
Chemical Substances	Histones ; Histone Demethylases (EC 1.14.11.-) ; RNA (63231-63-0) ; KDM4C protein, human ; Jumonji Domain-Containing Histone Demethylases (EC 1.14.11.-) ; PRDM9 protein, human (EC 2.1.1.43) ; Histone-Lysine N-Methyltransferase (EC 2.1.1.43)
Language	English
Publishing date	2023-02-01
Publishing country	Italy
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2333-4
ISSN	1592-8721 ; 0017-6567 ; 0390-6078
ISSN (online)	1592-8721
ISSN	0017-6567 ; 0390-6078
DOI	10.3324/haematol.2021.280005
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