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2. Cell-autonomous IL6ST activation suppresses prostate cancer development via STAT3/ARF/p53-driven senescence and confers an immune-active tumor microenvironment

Author

Sternberg, Christina, Raigel, Martin, Limberger, Tanja, Trachtová, Karolína, Schlederer, Michaela, Lindner, Desiree, Kodajova, Petra, Yang, Jiaye, Ziegler, Roman, Kalla, Jessica, Stoiber, Stefan, Dey, Saptaswa, Zwolanek, Daniela, Neubauer, Heidi A., Oberhuber, Monika, Redmer, Torben, Hejret, Václav, Tichy, Boris, Tomberger, Martina, Harbusch, Nora S., Pencik, Jan, Tangermann, Simone, Bystry, Vojtech, Persson, Jenny L., Egger, Gerda, Pospisilova, Sarka, Eferl, Robert, Wolf, Peter, Sternberg, Felix, Högler, Sandra, Lagger, Sabine, Rose-John, Stefan, and Kenner, Lukas

Published
2024
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3. JUN mediates the senescence associated secretory phenotype and immune cell recruitment to prevent prostate cancer progression

Author

Redmer, Torben, Raigel, Martin, Sternberg, Christina, Ziegler, Roman, Probst, Clara, Lindner, Desiree, Aufinger, Astrid, Limberger, Tanja, Trachtova, Karolina, Kodajova, Petra, Högler, Sandra, Schlederer, Michaela, Stoiber, Stefan, Oberhuber, Monika, Bolis, Marco, Neubauer, Heidi A., Miranda, Sara, Tomberger, Martina, Harbusch, Nora S., Garces de los Fayos Alonso, Ines, Sternberg, Felix, Moriggl, Richard, Theurillat, Jean-Philippe, Tichy, Boris, Bystry, Vojtech, Persson, Jenny L., Mathas, Stephan, Aberger, Fritz, Strobl, Birgit, Pospisilova, Sarka, Merkel, Olaf, Egger, Gerda, Lagger, Sabine, and Kenner, Lukas

Published
2024
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5. Real-World Performance of Integrative Clinical Genomics in Pediatric Precision Oncology

Author

Pokorna, Petra, Palova, Hana, Adamcova, Sona, Jugas, Robin, Al Tukmachi, Dagmar, Kyr, Michal, Knoflickova, Dana, Kozelkova, Katerina, Bystry, Vojtech, Mejstrikova, Sona, Merta, Tomas, Trachtova, Karolina, Podlipna, Eliska, Mudry, Peter, Pavelka, Zdenek, Bajciova, Viera, Tinka, Pavel, Jarosova, Marie, Catela Ivkovic, Tina, Madlener, Sibylle, Pal, Karol, Stepien, Natalia, Mayr, Lisa, Tichy, Boris, Drabova, Klara, Jezova, Marta, Kozakova, Sarka, Vanackova, Jitka, Radova, Lenka, Steininger, Karin, Haberler, Christine, Gojo, Johannes, Sterba, Jaroslav, and Slaby, Ondrej

Published
2024
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7. Mimicking Tumor Cell Heterogeneity of Colorectal Cancer in a Patient-derived Organoid-Fibroblast Model

Author

Atanasova, Velina S., de Jesus Cardona, Crhistian, Hejret, Václav, Tiefenbacher, Andreas, Mair, Theresia, Tran, Loan, Pfneissl, Janette, Draganić, Kristina, Binder, Carina, Kabiljo, Julijan, Clement, Janik, Woeran, Katharina, Neudert, Barbara, Wohlhaupter, Sabrina, Haase, Astrid, Domazet, Sandra, Hengstschläger, Markus, Mitterhauser, Markus, Müllauer, Leonhard, Tichý, Boris, Bergmann, Michael, Schweikert, Gabriele, Hartl, Markus, Dolznig, Helmut, and Egger, Gerda

Published
2023
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9. Unveiling the dynamics and molecular landscape of a rare chronic lymphocytic leukemia subpopulation driving refractoriness: insights from single‐cell RNA sequencing.

Author

Kurucova, Terezia, Reblova, Kamila, Janovska, Pavlina, Porc, Jakub Pawel, Navrkalova, Veronika, Pavlova, Sarka, Malcikova, Jitka, Plevova, Karla, Tichy, Boris, Doubek, Michael, Bryja, Vitezslav, Kotaskova, Jana, and Pospisilova, Sarka

Abstract

Early identification of resistant cancer cells is currently a major challenge, as their expansion leads to refractoriness. To capture the dynamics of these cells, we made a comprehensive analysis of disease progression and treatment response in a chronic lymphocytic leukemia (CLL) patient using a combination of single‐cell and bulk genomic methods. At diagnosis, the patient presented with unfavorable genetic markers, including notch receptor 1 (NOTCH1) mutation and loss(11q). The initial and subsequent treatment lines did not lead to a durable response and the patient developed refractory disease. Refractory CLL cells featured substantial dysregulation in B‐cell phenotypic markers such as human leukocyte antigen (HLA) genes, immunoglobulin (IG) genes, CD19 molecule (CD19), membrane spanning 4‐domains A1 (MS4A1; previously known as CD20), CD79a molecule (CD79A) and paired box 5 (PAX5), indicating B‐cell de‐differentiation and disease transformation. We described the clonal evolution and characterized in detail two cell populations that emerged during the refractory disease phase, differing in the presence of high genomic complexity. In addition, we successfully tracked the cells with high genomic complexity back to the time before treatment, where they formed a rare subpopulation. We have confirmed that single‐cell RNA sequencing enables the characterization of refractory cells and the monitoring of their development over time. [ABSTRACT FROM AUTHOR]

Published
2024
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12. Nuclear inclusions of pathogenic ataxin-1 induce oxidative stress and perturb the protein synthesis machinery

Author

Laidou, Stamatia, Alanis-Lobato, Gregorio, Pribyl, Jan, Raskó, Tamás, Tichy, Boris, Mikulasek, Kamil, Tsagiopoulou, Maria, Oppelt, Jan, Kastrinaki, Georgia, Lefaki, Maria, Singh, Manvendra, Zink, Annika, Chondrogianni, Niki, Psomopoulos, Fotis, Prigione, Alessandro, Ivics, Zoltán, Pospisilova, Sarka, Skladal, Petr, Izsvák, Zsuzsanna, Andrade-Navarro, Miguel A., and Petrakis, Spyros

Published
2020
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13. ERIC recommendations for TP53mutation analysis in chronic lymphocytic leukemia—2024 update

Author

Malcikova, Jitka, Pavlova, Sarka, Baliakas, Panagiotis, Chatzikonstantinou, Thomas, Tausch, Eugen, Catherwood, Mark, Rossi, Davide, Soussi, Thierry, Tichy, Boris, Kater, Arnon P., Niemann, Carsten U., Davi, Frederic, Gaidano, Gianluca, Stilgenbauer, Stephan, Rosenquist, Richard, Stamatopoulos, Kostas, Ghia, Paolo, and Pospisilova, Sarka

Abstract

In chronic lymphocytic leukemia (CLL), analysis of TP53aberrations (deletion and/or mutation) is a crucial part of treatment decision-making algorithms. Technological and treatment advances have resulted in the need for an update of the last recommendations for TP53analysis in CLL, published by ERIC, the European Research Initiative on CLL, in 2018. Based on the current knowledge of the relevance of low-burden TP53-mutated clones, a specific variant allele frequency (VAF) cut-off for reporting TP53mutations is no longer recommended, but instead, the need for thorough method validation by the reporting laboratory is emphasized. The result of TP53analyses should always be interpreted within the context of available laboratory and clinical information, treatment indication, and therapeutic options. Methodological aspects of introducing next-generation sequencing (NGS) in routine practice are discussed with a focus on reliable detection of low-burden clones. Furthermore, potential interpretation challenges are presented, and a simplified algorithm for the classification of TP53variants in CLL is provided, representing a consensus based on previously published guidelines. Finally, the reporting requirements are highlighted, including a template for clinical reports of TP53aberrations. These recommendations are intended to assist diagnosticians in the correct assessment of TP53mutation status, but also physicians in the appropriate understanding of the lab reports, thus decreasing the risk of misinterpretation and incorrect management of patients in routine practice whilst also leading to improved stratification of patients with CLL in clinical trials.

Published
2024
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15. Enabling the Implementation of Next-Generation Sequencing into Clinical Diagnosis: Nemhesys Project

Author

Hernández-Rivas, Jesús María, Serramito-Gómez, Inmaculada, Kallio, Saara, Cantalejo, Amparo, Kotaskova, Jana, Rodriguez, Ana E., Abáigar, María, Benito, Rocio, Dolnik, Anna, Catherwood, Mark, Blayney, Jaine, Tichý, Boris, Chalupová, Ivana, Dubois, Philippe, Lopez, Roberto, Barranquero, Carlos, Lorenzo, María Díaz, Leitzelman, Mylène, Adhikari, Sadiksha, Pospíšilová, Šárka, Bullinger, Lars, Mills, Ken I, and Heckman, Caroline A.

Published
2022
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22. Stereotyped B-cell receptors in one-third of chronic lymphocytic leukemia: a molecular classification with implications for targeted therapies

Author

Agathangelidis, Andreas, Darzentas, Nikos, Hadzidimitriou, Anastasia, Brochet, Xavier, Murray, Fiona, Yan, Xiao-Jie, Davis, Zadie, van Gastel-Mol, Ellen J., Tresoldi, Cristina, Chu, Charles C., Cahill, Nicola, Giudicelli, Veronique, Tichy, Boris, Pedersen, Lone Bredo, Foroni, Letizia, Bonello, Lisa, Janus, Agnieszka, Smedby, Karin, Anagnostopoulos, Achilles, Merle-Beral, Helene, Laoutaris, Nikolaos, Juliusson, Gunnar, di Celle, Paola Francia, Pospisilova, Sarka, Jurlander, Jesper, Geisler, Christian, Tsaftaris, Athanasios, Lefranc, Marie-Paule, Langerak, Anton W., Oscier, David Graham, Chiorazzi, Nicholas, Belessi, Chrysoula, Davi, Frederic, Rosenquist, Richard, Ghia, Paolo, and Stamatopoulos, Kostas

Published
2012
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23. Mimicking tumor cell heterogeneity of colorectal cancer in a patient-derived organoid-fibroblast model

Author

Atanasova, Velina S, primary, de Jesus Cardona, Crhistian, additional, Hejret, Vaclav, additional, Tiefenbacher, Andreas, additional, Tran, Loan, additional, Binder, Carina, additional, Mair, Theresia, additional, Kabiljo, Julijan, additional, Clement, Janik, additional, Woeran, Katharina, additional, Neudert, Barbara, additional, Hengstschläger, Markus, additional, Mitterhauser, Markus, additional, Müllauer, Leonhard, additional, Tichy, Boris, additional, Bergmann, Michael, additional, Schweikert, Gabriele, additional, Hartl, Markus, additional, Dolznig, Helmut, additional, and Egger, Gerda, additional

Published
2022
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29. Thyroid and androgen receptor signaling are antagonized by μ-Crystallin in prostate cancer

Author

Aksoy, Osman, Pencik, Jan, Hartenbach, Markus, Moazzami, Ali A, Schlederer, Michaela, Balber, Theresa, Varady, Adam, Philippe, Cecile, Baltzer, Pascal A, Mazumder, Bismoy, Whitchurch, Jonathan B, Roberts, Christopher J, Haitel, Andrea, Herac, Merima, Susani, Martin, Mitterhauser, Markus, Marculescu, Rodrig, Stangl-Kremser, Judith, Hassler, Melanie R, Kramer, Gero, Shariat, Shahrokh F, Turner, Suzanne D, Tichy, Boris, Oppelt, Jan, Pospisilova, Sarka, Hartenbach, Sabrina, Tangermann, Simone, Egger, Gerda, Neubauer, Heidi A, Moriggl, Richard, Culig, Zoran, Greiner, Georg, Hoermann, Gregor, Hacker, Marcus, Heery, David M, Merkel, Olaf, Kenner, Lukas, Aksoy, Osman [0000-0002-3068-455X], and Apollo - University of Cambridge Repository

Subjects
Male, μ-Crystallin, Down-Regulation, urologic and male genital diseases, Choline, Cohort Studies, PSMA-PET, androgen receptor, Cell Line, Tumor, Positron Emission Tomography Computed Tomography, mu-Crystallins, Humans, Metabolomics, Neoplasm Staging, Receptors, Thyroid Hormone, Sequence Analysis, RNA, Gene Expression Profiling, thyroid hormone receptor, Prostatic Neoplasms, prostate cancer, Prognosis, Crystallins, Gene Expression Regulation, Neoplastic, Receptors, Androgen, Tissue Array Analysis, PC-3 Cells, Triiodothyronine, Signal Transduction
Abstract

Androgen deprivation therapy (ADT) remains a key approach in the treatment of prostate cancer (PCa). However, PCa inevitably relapses and becomes ADT resistant. Besides androgens, there is evidence that thyroid hormone thyroxine (T4) and its active form 3,5,3'-triiodo-L-thyronine (T3) are involved in the progression of PCa. Epidemiologic evidences show a higher incidence of PCa in men with elevated thyroid hormone levels. The thyroid hormone binding protein μ-Crystallin (CRYM) mediates intracellular thyroid hormone action by sequestering T3 and blocks its binding to cognate receptors (TRα/TRβ) in target tissues. We show in our study that low CRYM expression levels in PCa patients are associated with early biochemical recurrence and poor prognosis. Moreover, we found a disease stage-specific expression of CRYM in PCa. CRYM counteracted thyroid and androgen signaling and blocked intracellular choline uptake. CRYM inversely correlated with [18F]fluoromethylcholine (FMC) levels in positron emission tomography/magnetic resonance imaging of PCa patients. Our data suggest CRYM as a novel antagonist of T3- and androgen-mediated signaling in PCa. The role of CRYM could therefore be an essential control mechanism for the prevention of aggressive PCa growth.

Published
2020
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30. Selective Activation of CNS and Reference PPARGC1A Promoters Is Associated with Distinct Gene Programs Relevant for Neurodegenerative Diseases

Author

Kwik, Markus, primary, Hainzl, Stefan, additional, Oppelt, Jan, additional, Tichy, Boris, additional, Koller, Ulrich, additional, Bernardinelli, Emanuele, additional, Steiner, Markus, additional, Zara, Greta, additional, Nofziger, Charity, additional, Weis, Serge, additional, Paulmichl, Markus, additional, Dossena, Silvia, additional, Patsch, Wolfgang, additional, and Soyal, Selma M., additional

Published
2021
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32. STAT3 and TP53 mutations associate with poor prognosis in anaplastic large cell lymphoma

Author

Lobello, Cosimo, primary, Tichy, Boris, additional, Bystry, Vojtech, additional, Radova, Lenka, additional, Filip, Daniel, additional, Mraz, Marek, additional, Montes-Mojarro, Ivonne-Aidee, additional, Prokoph, Nina, additional, Larose, Hugo, additional, Liang, Huan-Chang, additional, Sharma, Geeta G., additional, Mologni, Luca, additional, Belada, David, additional, Kamaradova, Katerina, additional, Fend, Falko, additional, Gambacorti-Passerini, Carlo, additional, Merkel, Olaf, additional, Turner, Suzanne D., additional, Janikova, Andrea, additional, and Pospisilova, Sarka, additional

Published
2020
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33. Thyroid and androgen receptor signaling are antagonized by μ‐Crystallin in prostate cancer

Author

Aksoy, Osman, primary, Pencik, Jan, additional, Hartenbach, Markus, additional, Moazzami, Ali A., additional, Schlederer, Michaela, additional, Balber, Theresa, additional, Varady, Adam, additional, Philippe, Cecile, additional, Baltzer, Pascal A., additional, Mazumder, Bismoy, additional, Whitchurch, Jonathan B., additional, Roberts, Christopher J., additional, Haitel, Andrea, additional, Herac, Merima, additional, Susani, Martin, additional, Mitterhauser, Markus, additional, Marculescu, Rodrig, additional, Stangl‐Kremser, Judith, additional, Hassler, Melanie R., additional, Kramer, Gero, additional, Shariat, Shahrokh F., additional, Turner, Suzanne D., additional, Tichy, Boris, additional, Oppelt, Jan, additional, Pospisilova, Sarka, additional, Hartenbach, Sabrina, additional, Tangermann, Simone, additional, Egger, Gerda, additional, Neubauer, Heidi A., additional, Moriggl, Richard, additional, Culig, Zoran, additional, Greiner, Georg, additional, Hoermann, Gregor, additional, Hacker, Marcus, additional, Heery, David M., additional, Merkel, Olaf, additional, and Kenner, Lukas, additional

Published
2020
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35. Testing of library preparation methods for transcriptome sequencing of real life glioblastoma and brain tissue specimens: A comparative study with special focus on long non-coding RNAs

Author

Vecera, Marek, primary, Sana, Jiri, additional, Oppelt, Jan, additional, Tichy, Boris, additional, Alena, Kopkova, additional, Lipina, Radim, additional, Smrcka, Martin, additional, Jancalek, Radim, additional, Hermanova, Marketa, additional, Kren, Leos, additional, and Slaby, Ondrej, additional

Published
2019
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36. Low-burden TP53mutations in CLL: clinical impact and clonal evolution within the context of different treatment options

Author

Malcikova, Jitka, Pavlova, Sarka, Barbara, Kunt Vonkova, Radova, Lenka, Plevova, Karla, Kotaskova, Jana, Pal, Karol, Dvorackova, Barbara, Zenatova, Marcela, Hynst, Jakub, Ondrouskova, Eva, Panovska, Anna, Brychtova, Yvona, Zavacka, Kristyna, Tichy, Boris, Tom, Nikola, Mayer, Jiri, Doubek, Michael, and Pospisilova, Sarka

Abstract

Patients with chronic lymphocytic leukemia (CLL) bearing TP53mutations experience chemorefractory disease and are therefore candidates for targeted therapy. However, the significance of low-burden TP53mutations with <10% variant allele frequency (VAF) remains a matter for debate. Herein, we describe clonal evolution scenarios of low-burden TP53mutations, the clinical impact of which we analyzed in a “real-world” CLL cohort. TP53status was assessed by targeted next-generation sequencing (NGS) in 511 patients entering first-line treatment with chemo- and/or immunotherapy and 159 patients in relapse before treatment with targeted agents. Within the pretherapy cohort, 16% of patients carried low-burden TP53mutations (0.1% to 10% VAF). Although their presence did not significantly shorten event-free survival after first-line therapy, it affected overall survival (OS). In a subgroup with TP53mutations of 1% to 10% VAF, the impact on OS was observed only in patients with unmutated IGHV who had not received targeted therapy, as patients benefited from switching to targeted agents, regardless of initial TP53mutational status. Analysis of the clonal evolution of low-burden TP53mutations showed that the highest expansion rates were associated with fludarabine, cyclophosphamide, and rituximab regimen in both first- and second-line treatments (median VAF increase, 14.8× and 11.8×, respectively) in contrast to treatment with less intense treatment regimens (1.6×) and no treatment (0.8×). In the relapse cohort, 33% of patients carried low-burden TP53mutations, which did not expand significantly upon targeted treatment (median VAF change, 1×). Sporadic cases of TP53mutations' clonal shifts were connected with the development of resistance-associated mutations. Altogether, our data support the incorporation of low-burden TP53variants in clinical decision making.

Published
2021
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37. Transcription Factor YY1 Can Control AID-mediated Mutagenesis

Author

Zaprazna, Kristina, Basu, Arindam, Tom, Nikola, Jha, Vibha, Hodawadekar, Suchita, Radova, Lenka, Malcikova, Jitka, Tichy, Boris, Pospisilova, Sarka, and Atchison, Michael L.

Subjects
Male, Mice, Knockout, B-Lymphocytes, Ubiquitination, Mice, Transgenic, Lymphocyte Activation, Immunoglobulin Class Switching, Article, Mice, Inbred C57BL, Mice, Mutagenesis, Cytidine Deaminase, Mutation, Animals, DNA Breaks, Double-Stranded, Female, Somatic Hypermutation, Immunoglobulin, YY1 Transcription Factor, Protein Binding
Abstract

Activation-induced cytidine deminase (AID) is crucial for controlling the immunoglobulin (Ig) diversification processes of somatic hypermutation (SHM) and class switch recombination (CSR). AID initiates these processes by deamination of cytosine, ultimately resulting in mutations or double strand DNA breaks needed for SHM and CSR. Levels of AID control mutation rates, and off-target non-Ig gene mutations can contribute to lymphomagenesis. Therefore, factors that control AID levels in the nucleus can regulate SHM and CSR, and may contribute to disease. We previously showed that transcription factor YY1 can regulate the level of AID in the nucleus and Ig CSR. Therefore, we hypothesized that conditional knock-out of YY1 would lead to reduction in AID localization at the Ig locus, and reduced AID-mediated mutations. Using mice that overexpress AID (IgκAID yy1f/f) or that express normal AID levels (yy1f/f), we found that conditional knock-out of YY1 results in reduced AID nuclear levels, reduced localization of AID to the Sμ switch region, and reduced AID-mediated mutations. We find that the mechanism of YY1 control of AID nuclear accumulation is likely due to YY1-AID physical interaction which blocks AID ubiquitination.

Published
2017

40. Analysis of Mutational Landscape in Systemic Anaplastic Large Cell Lymphoma Identifies Novel Prognostic Markers

Author

Lobello, Cosimo, Tichý, Boris, Bystrý, Vojtěch, Radova, Lenka, Filip, Daniel, Mraz, Marek, Montes Mojarro, Ivonne Aidee, Fend, Falko, Prokoph, Nina, Larose, Hugo, Turner, Suzanne, Liang, Huan-Chang, Merkel, Olaf, Kamarádová, Kateřina, Belada, David, Sharma, Geeta G, Mologni, Luca, Gambacorti-Passerini, Carlo, Janikova, Andrea, and Pospisilova, Sarka

Published
2019
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41. Low-Burden TP53 Mutations Occur in Chronic Phase of Myeloproliferative Neoplasms Regardless of Hydroxyurea Administration, Disease Type, and JAK2 Status

Author

Kubesova, Blanka, primary, Pavlova, Sarka, additional, Malcikova, Jitka, additional, Kabathova, Jitka, additional, Radova, Lenka, additional, Tom, Nikola, additional, Tichy, Boris, additional, Plevova, Karla, additional, Kantorova, Barbara, additional, Fiedorova, Kristyna, additional, Kissova, Jarmila, additional, Gisslinger, Bettina, additional, Gisslinger, Heinz, additional, Mayer, Jiri, additional, Kralovics, Robert, additional, Pospisilova, Sarka, additional, and Doubek, Michael, additional

Published
2016
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42. COBLL1,LPLandZAP70expression defines prognostic subgroups of chronic lymphocytic leukemia patients with high accuracy and correlates withIGHVmutational status

Author

Plesingerova, Hana, primary, Librova, Zuzana, additional, Plevova, Karla, additional, Libra, Antonin, additional, Tichy, Boris, additional, Skuhrova Francova, Hana, additional, Vrbacky, Filip, additional, Smolej, Lukas, additional, Mayer, Jiri, additional, Bryja, Vitezslav, additional, Doubek, Michael, additional, and Pospisilova, Sarka, additional

Published
2016
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43. Significance of immunoglobulin B-cell receptor features in tumor dynamics of chronic lymphocytic leukemia

Author

Pospíšilová Šárka, Brychtova Yvona, Plevová Karla, Tichy Boris, Pavlova Sarka, Skuhrova Francova Hana, Brazdilova Kamila, Burckova Katerina, and Doubek Michael

Subjects
CD20, Immunoglobulin B, Chronic lymphocytic leukemia, Immunology, Dynamics (mechanics), medicine, Cancer research, biology.protein, Immunology and Allergy, Biology, medicine.disease, Receptor
Published
2013
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44. Transcription factor YY1 can control AID‐mediated mutagenesis in mice.

Author

Zaprazna, Kristina, Basu, Arindam, Tom, Nikola, Jha, Vibha, Hodawadekar, Suchita, Radova, Lenka, Malcikova, Jitka, Tichy, Boris, Pospisilova, Sarka, and Atchison, Michael L.

Abstract

Abstract: Activation‐induced cytidine deminase (AID) is crucial for controlling the immunoglobulin (Ig) diversification processes of somatic hypermutation (SHM) and class switch recombination (CSR). AID initiates these processes by deamination of cytosine, ultimately resulting in mutations or double strand DNA breaks needed for SHM and CSR. Levels of AID control mutation rates, and off‐target non‐Ig gene mutations can contribute to lymphomagenesis. Therefore, factors that control AID levels in the nucleus can regulate SHM and CSR, and may contribute to disease. We previously showed that transcription factor YY1 can regulate the level of AID in the nucleus and Ig CSR. Therefore, we hypothesized that conditional knock‐out of YY1 would lead to reduction in AID localization at the Ig locus, and reduced AID‐mediated mutations. Using mice that overexpress AID (IgκAID yy1f/f) or that express normal AID levels (yy1f/f), we found that conditional knock‐out of YY1 results in reduced AID nuclear levels, reduced localization of AID to the Sμ switch region, and reduced AID‐mediated mutations. We find that the mechanism of YY1 control of AID nuclear accumulation is likely due to YY1‐AID physical interaction which blocks AID ubiquitination. [ABSTRACT FROM AUTHOR]

Published
2018
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46. Single Cell Analysis of IG Genes in CLL: Cases with Multiple IGH Rearrangements Are Constituted of Several Independent Clones Even When Indistinguishable By Flow Cytometry

Author

Brazdilova, Kamila, primary, Plevova, Karla, additional, Skuhrova Francova, Hana, additional, Kockova, Helena, additional, Chmelikova, Magdalena, additional, Borsky, Marek, additional, Burckova, Katerina, additional, Kantorova, Barbara, additional, Tichy, Boris, additional, Skabrahova, Hana, additional, Brychtova, Yvona, additional, Mayer, Jiri, additional, Doubek, Michael, additional, and Pospisilova, Sarka, additional

Published
2015
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47. Abstract 3084: MicroRNA involvement in DNA damage response and BCR signaling in malignant B cells

Author

Cerna, Katerina, primary, Oppelt, Jan, additional, Radova, Lenka, additional, Musilova, Katerina, additional, Seda, Vaclav, additional, Pavlasova, Gabriela, additional, Jez, Michal, additional, Tom, Nikola, additional, Pardy, Filip, additional, Malcikova, Jitka, additional, Plevova, Karla, additional, Tichy, Boris, additional, Brychtova, Yvona, additional, Doubek, Michael, additional, Trbusek, Martin, additional, Mayer, Jiri, additional, Koca, Jaroslav, additional, Calogero, Raffaele, additional, Pospisilova, Sarka, additional, and Mraz, Marek, additional

Published
2015
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48. Micro RNA and mesial temporal lobe epilepsy with hippocampal sclerosis: Whole mi RNome profiling of human hippocampus.

Author

Bencurova, Petra, Baloun, Jiri, Musilova, Katerina, Radova, Lenka, Tichy, Boris, Pail, Martin, Zeman, Martin, Brichtova, Eva, Hermanova, Marketa, Pospisilova, Sarka, Mraz, Marek, and Brazdil, Milan

Subjects
MICRORNA, TEMPORAL lobe epilepsy, HIPPOCAMPUS diseases, POLYMERASE chain reaction, RNA sequencing
Abstract

Objective Mesial temporal lobe epilepsy ( mTLE) is a severe neurological disorder characterized by recurrent seizures. mTLE is frequently accompanied by neurodegeneration in the hippocampus resulting in hippocampal sclerosis ( HS), the most common morphological correlate of drug resistance in mTLE patients. Incomplete knowledge of pathological changes in mTLE+ HS complicates its therapy. The pathological mechanism underlying mTLE+ HS may involve abnormal gene expression regulation, including posttranscriptional networks involving micro RNAs (mi RNAs). mi RNA expression deregulation has been reported in various disorders, including epilepsy. However, the mi RNA profile of mTLE+ HS is not completely known and needs to be addressed. Methods Here, we have focused on hippocampal mi RNA profiling in 33 mTLE+ HS patients and nine postmortem controls to reveal abnormally expressed mi RNAs. In this study, we significantly reduced technology-related bias (the most common source of false positivity in mi RNA profiling data) by combining two different mi RNA profiling methods, namely next generation sequencing and mi RNA-specific quantitative real-time polymerase chain reaction. Results These methods combined have identified and validated 20 mi RNAs with altered expression in the human epileptic hippocampus; 19 mi RNAs were up-regulated and one down-regulated in mTLE+ HS patients. Nine of these mi RNAs have not been previously associated with epilepsy, and 19 aberrantly expressed mi RNAs potentially regulate the targets and pathways linked with epilepsy (such as potassium channels, γ-aminobutyric acid, neurotrophin signaling, and axon guidance). Significance This study extends current knowledge of mi RNA-mediated gene expression regulation in mTLE+ HS by identifying mi RNAs with altered expression in mTLE+ HS, including nine novel abnormally expressed mi RNAs and their putative targets. These observations further encourage the potential of micro RNA-based biomarkers or therapies. [ABSTRACT FROM AUTHOR]

Published
2017
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49. COBLL1 , LPL and ZAP70 expression defines prognostic subgroups of chronic lymphocytic leukemia patients with high accuracy and correlates with IGHV mutational status.

Author

Plesingerova, Hana, Librova, Zuzana, Plevova, Karla, Libra, Antonin, Tichy, Boris, Skuhrova Francova, Hana, Vrbacky, Filip, Smolej, Lukas, Mayer, Jiri, Bryja, Vitezslav, Doubek, Michael, and Pospisilova, Sarka

Subjects
CHRONIC lymphocytic leukemia, GENETIC mutation, LYMPHOCYTIC leukemia, CANCER invasiveness, LEUKEMIA, PROGNOSIS, PATIENTS
Abstract

The clinical course of chronic lymphocytic leukemia (CLL) is highly variable. Patients with unmutatedIGHV(U-CLL) usually progress rapidly, whereas patients with mutatedIGHV(M-CLL) have a more indolent disease. The expression of several genes correlates closely with theIGHVmutational status and could be used to assess prognosis in CLL. We analyzed the prognostic relevance ofCOBLL1,LPL,andZAP70gene expression, which correlated withIGHVmutational status (p < 0.0001), in 117 CLL patients and established a prognostic parameter dividing the tested cohort according to the disease aggressiveness. Our prognostic parameter was validated on an independent cohort of 161 CLL patients and achieved a high accuracy (94%). Patients divided according to the prognostic parameter differ in overall survival and time to first treatment (p < 0.0001, HR  = 2.300/5.970, 95% CI: 1.587–3.450/4.621–15.86). Our approach provides a reliable alternative method to prognosis assessment viaIGHVmutational status analysis. [ABSTRACT FROM PUBLISHER]

Published
2017
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50. TP53 mutation analysis in chronic lymphocytic leukemia: comparison of different detection methods

Author

Kantorova, Barbara, primary, Malcikova, Jitka, additional, Smardova, Jana, additional, Pavlova, Sarka, additional, Trbusek, Martin, additional, Tom, Nikola, additional, Plevova, Karla, additional, Tichy, Boris, additional, Truong, Sim, additional, Diviskova, Eva, additional, Kotaskova, Jana, additional, Oltova, Alexandra, additional, Patten, Nancy, additional, Brychtova, Yvona, additional, Doubek, Michael, additional, Mayer, Jiri, additional, and Pospisilova, Sarka, additional

Published
2014
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