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PiggyBac transposon tools for recessive screening identify B-cell lymphoma drivers in mice
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Zeitschriftentitel: | Nature Communications |
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Personen und Körperschaften: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
In: | Nature Communications, 10, 2019, 1 |
Format: | E-Article |
Sprache: | Englisch |
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Springer Science and Business Media LLC
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author_facet |
Weber, Julia de la Rosa, Jorge Grove, Carolyn S. Schick, Markus Rad, Lena Baranov, Olga Strong, Alexander Pfaus, Anja Friedrich, Mathias J. Engleitner, Thomas Lersch, Robert Öllinger, Rupert Grau, Michael Menendez, Irene Gonzalez Martella, Manuela Kohlhofer, Ursula Banerjee, Ruby Turchaninova, Maria A. Scherger, Anna Hoffman, Gary J. Hess, Julia Kuhn, Laura B. Ammon, Tim Kim, Johnny Schneider, Günter Unger, Kristian Zimber-Strobl, Ursula Heikenwälder, Mathias Schmidt-Supprian, Marc Yang, Fengtang Saur, Dieter Liu, Pentao Steiger, Katja Chudakov, Dmitriy M. Lenz, Georg Quintanilla-Martinez, Leticia Keller, Ulrich Vassiliou, George S. Cadiñanos, Juan Bradley, Allan Rad, Roland Weber, Julia de la Rosa, Jorge Grove, Carolyn S. Schick, Markus Rad, Lena Baranov, Olga Strong, Alexander Pfaus, Anja Friedrich, Mathias J. Engleitner, Thomas Lersch, Robert Öllinger, Rupert Grau, Michael Menendez, Irene Gonzalez Martella, Manuela Kohlhofer, Ursula Banerjee, Ruby Turchaninova, Maria A. Scherger, Anna Hoffman, Gary J. Hess, Julia Kuhn, Laura B. Ammon, Tim Kim, Johnny Schneider, Günter Unger, Kristian Zimber-Strobl, Ursula Heikenwälder, Mathias Schmidt-Supprian, Marc Yang, Fengtang Saur, Dieter Liu, Pentao Steiger, Katja Chudakov, Dmitriy M. Lenz, Georg Quintanilla-Martinez, Leticia Keller, Ulrich Vassiliou, George S. Cadiñanos, Juan Bradley, Allan Rad, Roland |
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author |
Weber, Julia de la Rosa, Jorge Grove, Carolyn S. Schick, Markus Rad, Lena Baranov, Olga Strong, Alexander Pfaus, Anja Friedrich, Mathias J. Engleitner, Thomas Lersch, Robert Öllinger, Rupert Grau, Michael Menendez, Irene Gonzalez Martella, Manuela Kohlhofer, Ursula Banerjee, Ruby Turchaninova, Maria A. Scherger, Anna Hoffman, Gary J. Hess, Julia Kuhn, Laura B. Ammon, Tim Kim, Johnny Schneider, Günter Unger, Kristian Zimber-Strobl, Ursula Heikenwälder, Mathias Schmidt-Supprian, Marc Yang, Fengtang Saur, Dieter Liu, Pentao Steiger, Katja Chudakov, Dmitriy M. Lenz, Georg Quintanilla-Martinez, Leticia Keller, Ulrich Vassiliou, George S. Cadiñanos, Juan Bradley, Allan Rad, Roland |
spellingShingle |
Weber, Julia de la Rosa, Jorge Grove, Carolyn S. Schick, Markus Rad, Lena Baranov, Olga Strong, Alexander Pfaus, Anja Friedrich, Mathias J. Engleitner, Thomas Lersch, Robert Öllinger, Rupert Grau, Michael Menendez, Irene Gonzalez Martella, Manuela Kohlhofer, Ursula Banerjee, Ruby Turchaninova, Maria A. Scherger, Anna Hoffman, Gary J. Hess, Julia Kuhn, Laura B. Ammon, Tim Kim, Johnny Schneider, Günter Unger, Kristian Zimber-Strobl, Ursula Heikenwälder, Mathias Schmidt-Supprian, Marc Yang, Fengtang Saur, Dieter Liu, Pentao Steiger, Katja Chudakov, Dmitriy M. Lenz, Georg Quintanilla-Martinez, Leticia Keller, Ulrich Vassiliou, George S. Cadiñanos, Juan Bradley, Allan Rad, Roland Nature Communications PiggyBac transposon tools for recessive screening identify B-cell lymphoma drivers in mice General Physics and Astronomy General Biochemistry, Genetics and Molecular Biology General Chemistry Multidisciplinary |
author_sort |
weber, julia |
spelling |
Weber, Julia de la Rosa, Jorge Grove, Carolyn S. Schick, Markus Rad, Lena Baranov, Olga Strong, Alexander Pfaus, Anja Friedrich, Mathias J. Engleitner, Thomas Lersch, Robert Öllinger, Rupert Grau, Michael Menendez, Irene Gonzalez Martella, Manuela Kohlhofer, Ursula Banerjee, Ruby Turchaninova, Maria A. Scherger, Anna Hoffman, Gary J. Hess, Julia Kuhn, Laura B. Ammon, Tim Kim, Johnny Schneider, Günter Unger, Kristian Zimber-Strobl, Ursula Heikenwälder, Mathias Schmidt-Supprian, Marc Yang, Fengtang Saur, Dieter Liu, Pentao Steiger, Katja Chudakov, Dmitriy M. Lenz, Georg Quintanilla-Martinez, Leticia Keller, Ulrich Vassiliou, George S. Cadiñanos, Juan Bradley, Allan Rad, Roland 2041-1723 Springer Science and Business Media LLC General Physics and Astronomy General Biochemistry, Genetics and Molecular Biology General Chemistry Multidisciplinary http://dx.doi.org/10.1038/s41467-019-09180-3 <jats:title>Abstract</jats:title><jats:p>B-cell lymphoma (BCL) is the most common hematologic malignancy. While sequencing studies gave insights into BCL genetics, identification of non-mutated cancer genes remains challenging. Here, we describe <jats:italic>PiggyBac</jats:italic> transposon tools and mouse models for recessive screening and show their application to study clonal B-cell lymphomagenesis. In a genome-wide screen, we discover BCL genes related to diverse molecular processes, including signaling, transcriptional regulation, chromatin regulation, or RNA metabolism. Cross-species analyses show the efficiency of the screen to pinpoint human cancer drivers altered by non-genetic mechanisms, including clinically relevant genes dysregulated epigenetically, transcriptionally, or post-transcriptionally in human BCL. We also describe a CRISPR/Cas9-based <jats:italic>in vivo</jats:italic> platform for BCL functional genomics, and validate discovered genes, such as <jats:italic>Rfx7</jats:italic>, a transcription factor, and <jats:italic>Phip</jats:italic>, a chromatin regulator, which suppress lymphomagenesis in mice. Our study gives comprehensive insights into the molecular landscapes of BCL and underlines the power of genome-scale screening to inform biology.</jats:p> PiggyBac transposon tools for recessive screening identify B-cell lymphoma drivers in mice Nature Communications |
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title |
PiggyBac transposon tools for recessive screening identify B-cell lymphoma drivers in mice |
title_unstemmed |
PiggyBac transposon tools for recessive screening identify B-cell lymphoma drivers in mice |
title_full |
PiggyBac transposon tools for recessive screening identify B-cell lymphoma drivers in mice |
title_fullStr |
PiggyBac transposon tools for recessive screening identify B-cell lymphoma drivers in mice |
title_full_unstemmed |
PiggyBac transposon tools for recessive screening identify B-cell lymphoma drivers in mice |
title_short |
PiggyBac transposon tools for recessive screening identify B-cell lymphoma drivers in mice |
title_sort |
piggybac transposon tools for recessive screening identify b-cell lymphoma drivers in mice |
topic |
General Physics and Astronomy General Biochemistry, Genetics and Molecular Biology General Chemistry Multidisciplinary |
url |
http://dx.doi.org/10.1038/s41467-019-09180-3 |
publishDate |
2019 |
physical |
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<jats:title>Abstract</jats:title><jats:p>B-cell lymphoma (BCL) is the most common hematologic malignancy. While sequencing studies gave insights into BCL genetics, identification of non-mutated cancer genes remains challenging. Here, we describe <jats:italic>PiggyBac</jats:italic> transposon tools and mouse models for recessive screening and show their application to study clonal B-cell lymphomagenesis. In a genome-wide screen, we discover BCL genes related to diverse molecular processes, including signaling, transcriptional regulation, chromatin regulation, or RNA metabolism. Cross-species analyses show the efficiency of the screen to pinpoint human cancer drivers altered by non-genetic mechanisms, including clinically relevant genes dysregulated epigenetically, transcriptionally, or post-transcriptionally in human BCL. We also describe a CRISPR/Cas9-based <jats:italic>in vivo</jats:italic> platform for BCL functional genomics, and validate discovered genes, such as <jats:italic>Rfx7</jats:italic>, a transcription factor, and <jats:italic>Phip</jats:italic>, a chromatin regulator, which suppress lymphomagenesis in mice. Our study gives comprehensive insights into the molecular landscapes of BCL and underlines the power of genome-scale screening to inform biology.</jats:p> |
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author | Weber, Julia, de la Rosa, Jorge, Grove, Carolyn S., Schick, Markus, Rad, Lena, Baranov, Olga, Strong, Alexander, Pfaus, Anja, Friedrich, Mathias J., Engleitner, Thomas, Lersch, Robert, Öllinger, Rupert, Grau, Michael, Menendez, Irene Gonzalez, Martella, Manuela, Kohlhofer, Ursula, Banerjee, Ruby, Turchaninova, Maria A., Scherger, Anna, Hoffman, Gary J., Hess, Julia, Kuhn, Laura B., Ammon, Tim, Kim, Johnny, Schneider, Günter, Unger, Kristian, Zimber-Strobl, Ursula, Heikenwälder, Mathias, Schmidt-Supprian, Marc, Yang, Fengtang, Saur, Dieter, Liu, Pentao, Steiger, Katja, Chudakov, Dmitriy M., Lenz, Georg, Quintanilla-Martinez, Leticia, Keller, Ulrich, Vassiliou, George S., Cadiñanos, Juan, Bradley, Allan, Rad, Roland |
author_facet | Weber, Julia, de la Rosa, Jorge, Grove, Carolyn S., Schick, Markus, Rad, Lena, Baranov, Olga, Strong, Alexander, Pfaus, Anja, Friedrich, Mathias J., Engleitner, Thomas, Lersch, Robert, Öllinger, Rupert, Grau, Michael, Menendez, Irene Gonzalez, Martella, Manuela, Kohlhofer, Ursula, Banerjee, Ruby, Turchaninova, Maria A., Scherger, Anna, Hoffman, Gary J., Hess, Julia, Kuhn, Laura B., Ammon, Tim, Kim, Johnny, Schneider, Günter, Unger, Kristian, Zimber-Strobl, Ursula, Heikenwälder, Mathias, Schmidt-Supprian, Marc, Yang, Fengtang, Saur, Dieter, Liu, Pentao, Steiger, Katja, Chudakov, Dmitriy M., Lenz, Georg, Quintanilla-Martinez, Leticia, Keller, Ulrich, Vassiliou, George S., Cadiñanos, Juan, Bradley, Allan, Rad, Roland, Weber, Julia, de la Rosa, Jorge, Grove, Carolyn S., Schick, Markus, Rad, Lena, Baranov, Olga, Strong, Alexander, Pfaus, Anja, Friedrich, Mathias J., Engleitner, Thomas, Lersch, Robert, Öllinger, Rupert, Grau, Michael, Menendez, Irene Gonzalez, Martella, Manuela, Kohlhofer, Ursula, Banerjee, Ruby, Turchaninova, Maria A., Scherger, Anna, Hoffman, Gary J., Hess, Julia, Kuhn, Laura B., Ammon, Tim, Kim, Johnny, Schneider, Günter, Unger, Kristian, Zimber-Strobl, Ursula, Heikenwälder, Mathias, Schmidt-Supprian, Marc, Yang, Fengtang, Saur, Dieter, Liu, Pentao, Steiger, Katja, Chudakov, Dmitriy M., Lenz, Georg, Quintanilla-Martinez, Leticia, Keller, Ulrich, Vassiliou, George S., Cadiñanos, Juan, Bradley, Allan, Rad, Roland |
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description | <jats:title>Abstract</jats:title><jats:p>B-cell lymphoma (BCL) is the most common hematologic malignancy. While sequencing studies gave insights into BCL genetics, identification of non-mutated cancer genes remains challenging. Here, we describe <jats:italic>PiggyBac</jats:italic> transposon tools and mouse models for recessive screening and show their application to study clonal B-cell lymphomagenesis. In a genome-wide screen, we discover BCL genes related to diverse molecular processes, including signaling, transcriptional regulation, chromatin regulation, or RNA metabolism. Cross-species analyses show the efficiency of the screen to pinpoint human cancer drivers altered by non-genetic mechanisms, including clinically relevant genes dysregulated epigenetically, transcriptionally, or post-transcriptionally in human BCL. We also describe a CRISPR/Cas9-based <jats:italic>in vivo</jats:italic> platform for BCL functional genomics, and validate discovered genes, such as <jats:italic>Rfx7</jats:italic>, a transcription factor, and <jats:italic>Phip</jats:italic>, a chromatin regulator, which suppress lymphomagenesis in mice. Our study gives comprehensive insights into the molecular landscapes of BCL and underlines the power of genome-scale screening to inform biology.</jats:p> |
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spelling | Weber, Julia de la Rosa, Jorge Grove, Carolyn S. Schick, Markus Rad, Lena Baranov, Olga Strong, Alexander Pfaus, Anja Friedrich, Mathias J. Engleitner, Thomas Lersch, Robert Öllinger, Rupert Grau, Michael Menendez, Irene Gonzalez Martella, Manuela Kohlhofer, Ursula Banerjee, Ruby Turchaninova, Maria A. Scherger, Anna Hoffman, Gary J. Hess, Julia Kuhn, Laura B. Ammon, Tim Kim, Johnny Schneider, Günter Unger, Kristian Zimber-Strobl, Ursula Heikenwälder, Mathias Schmidt-Supprian, Marc Yang, Fengtang Saur, Dieter Liu, Pentao Steiger, Katja Chudakov, Dmitriy M. Lenz, Georg Quintanilla-Martinez, Leticia Keller, Ulrich Vassiliou, George S. Cadiñanos, Juan Bradley, Allan Rad, Roland 2041-1723 Springer Science and Business Media LLC General Physics and Astronomy General Biochemistry, Genetics and Molecular Biology General Chemistry Multidisciplinary http://dx.doi.org/10.1038/s41467-019-09180-3 <jats:title>Abstract</jats:title><jats:p>B-cell lymphoma (BCL) is the most common hematologic malignancy. While sequencing studies gave insights into BCL genetics, identification of non-mutated cancer genes remains challenging. Here, we describe <jats:italic>PiggyBac</jats:italic> transposon tools and mouse models for recessive screening and show their application to study clonal B-cell lymphomagenesis. In a genome-wide screen, we discover BCL genes related to diverse molecular processes, including signaling, transcriptional regulation, chromatin regulation, or RNA metabolism. Cross-species analyses show the efficiency of the screen to pinpoint human cancer drivers altered by non-genetic mechanisms, including clinically relevant genes dysregulated epigenetically, transcriptionally, or post-transcriptionally in human BCL. We also describe a CRISPR/Cas9-based <jats:italic>in vivo</jats:italic> platform for BCL functional genomics, and validate discovered genes, such as <jats:italic>Rfx7</jats:italic>, a transcription factor, and <jats:italic>Phip</jats:italic>, a chromatin regulator, which suppress lymphomagenesis in mice. Our study gives comprehensive insights into the molecular landscapes of BCL and underlines the power of genome-scale screening to inform biology.</jats:p> PiggyBac transposon tools for recessive screening identify B-cell lymphoma drivers in mice Nature Communications |
spellingShingle | Weber, Julia, de la Rosa, Jorge, Grove, Carolyn S., Schick, Markus, Rad, Lena, Baranov, Olga, Strong, Alexander, Pfaus, Anja, Friedrich, Mathias J., Engleitner, Thomas, Lersch, Robert, Öllinger, Rupert, Grau, Michael, Menendez, Irene Gonzalez, Martella, Manuela, Kohlhofer, Ursula, Banerjee, Ruby, Turchaninova, Maria A., Scherger, Anna, Hoffman, Gary J., Hess, Julia, Kuhn, Laura B., Ammon, Tim, Kim, Johnny, Schneider, Günter, Unger, Kristian, Zimber-Strobl, Ursula, Heikenwälder, Mathias, Schmidt-Supprian, Marc, Yang, Fengtang, Saur, Dieter, Liu, Pentao, Steiger, Katja, Chudakov, Dmitriy M., Lenz, Georg, Quintanilla-Martinez, Leticia, Keller, Ulrich, Vassiliou, George S., Cadiñanos, Juan, Bradley, Allan, Rad, Roland, Nature Communications, PiggyBac transposon tools for recessive screening identify B-cell lymphoma drivers in mice, General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry, Multidisciplinary |
title | PiggyBac transposon tools for recessive screening identify B-cell lymphoma drivers in mice |
title_full | PiggyBac transposon tools for recessive screening identify B-cell lymphoma drivers in mice |
title_fullStr | PiggyBac transposon tools for recessive screening identify B-cell lymphoma drivers in mice |
title_full_unstemmed | PiggyBac transposon tools for recessive screening identify B-cell lymphoma drivers in mice |
title_short | PiggyBac transposon tools for recessive screening identify B-cell lymphoma drivers in mice |
title_sort | piggybac transposon tools for recessive screening identify b-cell lymphoma drivers in mice |
title_unstemmed | PiggyBac transposon tools for recessive screening identify B-cell lymphoma drivers in mice |
topic | General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry, Multidisciplinary |
url | http://dx.doi.org/10.1038/s41467-019-09180-3 |