Search

Your search keyword '"Simonis, Marieke"' showing total 35 results
Start Over Author "Simonis, Marieke" Publication Type Electronic Resources
35 results on '"Simonis, Marieke"'

1. Robust detection of translocations in lymphoma FFPE samples using targeted locus capture-based sequencing

Author

Allahyar, Amin, Pieterse, Mark, Swennenhuis, Joost, Los-de Vries, G Tjitske, Yilmaz, Mehmet, Leguit, Roos, Meijers, Ruud W J, van der Geize, Robert, Vermaat, Joost, Cleven, Arjen, van Wezel, Tom, Diepstra, Arjan, van Kempen, Léon C, Hijmering, Nathalie J, Stathi, Phylicia, Sharma, Milan, Melquiond, Adrien S J, de Vree, Paula J P, Verstegen, Marjon J A M, Krijger, Peter H L, Hajo, Karima, Simonis, Marieke, Rakszewska, Agata, van Min, Max, de Jong, Daphne, Ylstra, Bauke, Feitsma, Harma, Splinter, Erik, de Laat, Wouter, Allahyar, Amin, Pieterse, Mark, Swennenhuis, Joost, Los-de Vries, G Tjitske, Yilmaz, Mehmet, Leguit, Roos, Meijers, Ruud W J, van der Geize, Robert, Vermaat, Joost, Cleven, Arjen, van Wezel, Tom, Diepstra, Arjan, van Kempen, Léon C, Hijmering, Nathalie J, Stathi, Phylicia, Sharma, Milan, Melquiond, Adrien S J, de Vree, Paula J P, Verstegen, Marjon J A M, Krijger, Peter H L, Hajo, Karima, Simonis, Marieke, Rakszewska, Agata, van Min, Max, de Jong, Daphne, Ylstra, Bauke, Feitsma, Harma, Splinter, Erik, and de Laat, Wouter

Abstract

In routine diagnostic pathology, cancer biopsies are preserved by formalin-fixed, paraffin-embedding (FFPE) procedures for examination of (intra-) cellular morphology. Such procedures inadvertently induce DNA fragmentation, which compromises sequencing-based analyses of chromosomal rearrangements. Yet, rearrangements drive many types of hematolymphoid malignancies and solid tumors, and their manifestation is instructive for diagnosis, prognosis, and treatment. Here, we present FFPE-targeted locus capture (FFPE-TLC) for targeted sequencing of proximity-ligation products formed in FFPE tissue blocks, and PLIER, a computational framework that allows automated identification and characterization of rearrangements involving selected, clinically relevant, loci. FFPE-TLC, blindly applied to 149 lymphoma and control FFPE samples, identifies the known and previously uncharacterized rearrangement partners. It outperforms fluorescence in situ hybridization (FISH) in sensitivity and specificity, and shows clear advantages over standard capture-NGS methods, finding rearrangements involving repetitive sequences which they typically miss. FFPE-TLC is therefore a powerful clinical diagnostics tool for accurate targeted rearrangement detection in FFPE specimens.

Published
2021

2. Robust detection of translocations in lymphoma FFPE samples using targeted locus capture-based sequencing

Author

Allahyar, Amin, Pieterse, Mark, Swennenhuis, Joost, Los-de Vries, G Tjitske, Yilmaz, Mehmet, Leguit, Roos, Meijers, Ruud W J, van der Geize, Robert, Vermaat, Joost, Cleven, Arjen, van Wezel, Tom, Diepstra, Arjan, van Kempen, Léon C, Hijmering, Nathalie J, Stathi, Phylicia, Sharma, Milan, Melquiond, Adrien S J, de Vree, Paula J P, Verstegen, Marjon J A M, Krijger, Peter H L, Hajo, Karima, Simonis, Marieke, Rakszewska, Agata, van Min, Max, de Jong, Daphne, Ylstra, Bauke, Feitsma, Harma, Splinter, Erik, de Laat, Wouter, Allahyar, Amin, Pieterse, Mark, Swennenhuis, Joost, Los-de Vries, G Tjitske, Yilmaz, Mehmet, Leguit, Roos, Meijers, Ruud W J, van der Geize, Robert, Vermaat, Joost, Cleven, Arjen, van Wezel, Tom, Diepstra, Arjan, van Kempen, Léon C, Hijmering, Nathalie J, Stathi, Phylicia, Sharma, Milan, Melquiond, Adrien S J, de Vree, Paula J P, Verstegen, Marjon J A M, Krijger, Peter H L, Hajo, Karima, Simonis, Marieke, Rakszewska, Agata, van Min, Max, de Jong, Daphne, Ylstra, Bauke, Feitsma, Harma, Splinter, Erik, and de Laat, Wouter

Abstract

In routine diagnostic pathology, cancer biopsies are preserved by formalin-fixed, paraffin-embedding (FFPE) procedures for examination of (intra-) cellular morphology. Such procedures inadvertently induce DNA fragmentation, which compromises sequencing-based analyses of chromosomal rearrangements. Yet, rearrangements drive many types of hematolymphoid malignancies and solid tumors, and their manifestation is instructive for diagnosis, prognosis, and treatment. Here, we present FFPE-targeted locus capture (FFPE-TLC) for targeted sequencing of proximity-ligation products formed in FFPE tissue blocks, and PLIER, a computational framework that allows automated identification and characterization of rearrangements involving selected, clinically relevant, loci. FFPE-TLC, blindly applied to 149 lymphoma and control FFPE samples, identifies the known and previously uncharacterized rearrangement partners. It outperforms fluorescence in situ hybridization (FISH) in sensitivity and specificity, and shows clear advantages over standard capture-NGS methods, finding rearrangements involving repetitive sequences which they typically miss. FFPE-TLC is therefore a powerful clinical diagnostics tool for accurate targeted rearrangement detection in FFPE specimens.

Published
2021

3. Robust detection of translocations in lymphoma FFPE samples using targeted locus capture-based sequencing

Author

CMM Groep De Ridder, Cancer, CMM Groep Kloosterman, Pathologie Pathologen staf, Pathologie Moleculair, CMM Onderwijs, Pathologie Moleculair Path., CMM Groep Burgering, Genetica, Hubrecht Institute with UMC, Allahyar, Amin, Pieterse, Mark, Swennenhuis, Joost, Los-de Vries, G. Tjitske, Yilmaz, Mehmet, Leguit, Roos, Meijers, Ruud W.J., van der Geize, Robert, Vermaat, Joost, Cleven, Arjen, van Wezel, Tom, Diepstra, Arjan, van Kempen, Léon C., Hijmering, Nathalie J., Stathi, Phylicia, Sharma, Milan, Melquiond, Adrien S.J., de Vree, Paula J.P., Verstegen, Marjon J.A.M., Krijger, Peter H.L., Hajo, Karima, Simonis, Marieke, Rakszewska, Agata, van Min, Max, de Jong, Daphne, Ylstra, Bauke, Feitsma, Harma, Splinter, Erik, de Laat, Wouter, CMM Groep De Ridder, Cancer, CMM Groep Kloosterman, Pathologie Pathologen staf, Pathologie Moleculair, CMM Onderwijs, Pathologie Moleculair Path., CMM Groep Burgering, Genetica, Hubrecht Institute with UMC, Allahyar, Amin, Pieterse, Mark, Swennenhuis, Joost, Los-de Vries, G. Tjitske, Yilmaz, Mehmet, Leguit, Roos, Meijers, Ruud W.J., van der Geize, Robert, Vermaat, Joost, Cleven, Arjen, van Wezel, Tom, Diepstra, Arjan, van Kempen, Léon C., Hijmering, Nathalie J., Stathi, Phylicia, Sharma, Milan, Melquiond, Adrien S.J., de Vree, Paula J.P., Verstegen, Marjon J.A.M., Krijger, Peter H.L., Hajo, Karima, Simonis, Marieke, Rakszewska, Agata, van Min, Max, de Jong, Daphne, Ylstra, Bauke, Feitsma, Harma, Splinter, Erik, and de Laat, Wouter

Published
2021

4. TEG001 Insert Integrity from Vector Producer Cells until Medicinal Product

Author

Straetemans, Trudy, Janssen, Anke, Jansen, Koen, Doorn, Ruud, Aarts, Tineke, van Muyden, Anna D D, Simonis, Marieke, Bergboer, Judith, de Witte, Moniek, Sebestyen, Zsolt, Kuball, Jurgen, Straetemans, Trudy, Janssen, Anke, Jansen, Koen, Doorn, Ruud, Aarts, Tineke, van Muyden, Anna D D, Simonis, Marieke, Bergboer, Judith, de Witte, Moniek, Sebestyen, Zsolt, and Kuball, Jurgen

Published
2020

5. TEG001 Insert Integrity from Vector Producer Cells until Medicinal Product

Author

Straetemans, Trudy, Janssen, Anke, Jansen, Koen, Doorn, Ruud, Aarts, Tineke, van Muyden, Anna D D, Simonis, Marieke, Bergboer, Judith, de Witte, Moniek, Sebestyen, Zsolt, Kuball, Jurgen, Straetemans, Trudy, Janssen, Anke, Jansen, Koen, Doorn, Ruud, Aarts, Tineke, van Muyden, Anna D D, Simonis, Marieke, Bergboer, Judith, de Witte, Moniek, Sebestyen, Zsolt, and Kuball, Jurgen

Published
2020

6. TEG001 Insert Integrity from Vector Producer Cells until Medicinal Product

Author

Straetemans, Trudy, Janssen, Anke, Jansen, Koen, Doorn, Ruud, Aarts, Tineke, van Muyden, Anna D D, Simonis, Marieke, Bergboer, Judith, de Witte, Moniek, Sebestyen, Zsolt, Kuball, Jurgen, Straetemans, Trudy, Janssen, Anke, Jansen, Koen, Doorn, Ruud, Aarts, Tineke, van Muyden, Anna D D, Simonis, Marieke, Bergboer, Judith, de Witte, Moniek, Sebestyen, Zsolt, and Kuball, Jurgen

Published
2020

7. TEG001 Insert Integrity from Vector Producer Cells until Medicinal Product

Author

CTI Kuball, Unit Opleiding Aios, MS Hematologie, Infection & Immunity, Regenerative Medicine and Stem Cells, Cancer, Straetemans, Trudy, Janssen, Anke, Jansen, Koen, Doorn, Ruud, Aarts, Tineke, van Muyden, Anna D D, Simonis, Marieke, Bergboer, Judith, de Witte, Moniek, Sebestyen, Zsolt, Kuball, Jurgen, CTI Kuball, Unit Opleiding Aios, MS Hematologie, Infection & Immunity, Regenerative Medicine and Stem Cells, Cancer, Straetemans, Trudy, Janssen, Anke, Jansen, Koen, Doorn, Ruud, Aarts, Tineke, van Muyden, Anna D D, Simonis, Marieke, Bergboer, Judith, de Witte, Moniek, Sebestyen, Zsolt, and Kuball, Jurgen

Published
2020

8. Molecular dissection of germline chromothripsis in a developmental context using patient-derived iPS cells

Author

Middelkamp, Sjors, van Heesch, S.A.A.C., Braat, Koen, de Ligt, J, van Iterson, Maarten, Simonis, Marieke, van Roosmalen, Markus J., Kelder, Martijn J E, Kruisselbrink, Evelien, Hochstenbach, Ron, Verbeek, Nienke, Ippel, Elly, Adolfs, Y., Pasterkamp, R. Jeroen, Kloosterman, Wigard P., Kuijk, Ewart W., Cuppen, Edwin, Middelkamp, Sjors, van Heesch, S.A.A.C., Braat, Koen, de Ligt, J, van Iterson, Maarten, Simonis, Marieke, van Roosmalen, Markus J., Kelder, Martijn J E, Kruisselbrink, Evelien, Hochstenbach, Ron, Verbeek, Nienke, Ippel, Elly, Adolfs, Y., Pasterkamp, R. Jeroen, Kloosterman, Wigard P., Kuijk, Ewart W., and Cuppen, Edwin

Published
2017

9. Molecular dissection of germline chromothripsis in a developmental context using patient-derived iPS cells

Author

Middelkamp, Sjors, van Heesch, S.A.A.C., Braat, Koen, de Ligt, J, van Iterson, Maarten, Simonis, Marieke, van Roosmalen, Markus J., Kelder, Martijn J E, Kruisselbrink, Evelien, Hochstenbach, Ron, Verbeek, Nienke, Ippel, Elly, Adolfs, Y., Pasterkamp, R. Jeroen, Kloosterman, Wigard P., Kuijk, Ewart W., Cuppen, Edwin, Middelkamp, Sjors, van Heesch, S.A.A.C., Braat, Koen, de Ligt, J, van Iterson, Maarten, Simonis, Marieke, van Roosmalen, Markus J., Kelder, Martijn J E, Kruisselbrink, Evelien, Hochstenbach, Ron, Verbeek, Nienke, Ippel, Elly, Adolfs, Y., Pasterkamp, R. Jeroen, Kloosterman, Wigard P., Kuijk, Ewart W., and Cuppen, Edwin

Published
2017

10. Molecular dissection of germline chromothripsis in a developmental context using patient-derived iPS cells

Author

Middelkamp, Sjors, van Heesch, S.A.A.C., Braat, Koen, de Ligt, J, van Iterson, Maarten, Simonis, Marieke, van Roosmalen, Markus J., Kelder, Martijn J E, Kruisselbrink, Evelien, Hochstenbach, Ron, Verbeek, Nienke, Ippel, Elly, Adolfs, Y., Pasterkamp, R. Jeroen, Kloosterman, Wigard P., Kuijk, Ewart W., Cuppen, Edwin, Middelkamp, Sjors, van Heesch, S.A.A.C., Braat, Koen, de Ligt, J, van Iterson, Maarten, Simonis, Marieke, van Roosmalen, Markus J., Kelder, Martijn J E, Kruisselbrink, Evelien, Hochstenbach, Ron, Verbeek, Nienke, Ippel, Elly, Adolfs, Y., Pasterkamp, R. Jeroen, Kloosterman, Wigard P., Kuijk, Ewart W., and Cuppen, Edwin

Published
2017

11. Molecular dissection of germline chromothripsis in a developmental context using patient-derived iPS cells

Author

CMM Groep Cuppen, Cancer, CMM Groep Coffer, Regenerative Medicine and Stem Cells, Child Health, CMM Groep Kloosterman, CTI, Genetica Sectie Genoomdiagnostiek, Brain, Genetica Klinische Genetica, TN groep Pasterkamp, Circulatory Health, Middelkamp, Sjors, van Heesch, S.A.A.C., Braat, Koen, de Ligt, J, van Iterson, Maarten, Simonis, Marieke, van Roosmalen, Markus J., Kelder, Martijn J E, Kruisselbrink, Evelien, Hochstenbach, Ron, Verbeek, Nienke, Ippel, Elly, Adolfs, Y., Pasterkamp, R. Jeroen, Kloosterman, Wigard P., Kuijk, Ewart W., Cuppen, Edwin, CMM Groep Cuppen, Cancer, CMM Groep Coffer, Regenerative Medicine and Stem Cells, Child Health, CMM Groep Kloosterman, CTI, Genetica Sectie Genoomdiagnostiek, Brain, Genetica Klinische Genetica, TN groep Pasterkamp, Circulatory Health, Middelkamp, Sjors, van Heesch, S.A.A.C., Braat, Koen, de Ligt, J, van Iterson, Maarten, Simonis, Marieke, van Roosmalen, Markus J., Kelder, Martijn J E, Kruisselbrink, Evelien, Hochstenbach, Ron, Verbeek, Nienke, Ippel, Elly, Adolfs, Y., Pasterkamp, R. Jeroen, Kloosterman, Wigard P., Kuijk, Ewart W., and Cuppen, Edwin

Published
2017

15. The genomic scrapheap challenge; extracting relevant data from unmapped whole genome sequencing reads, including strain specific genomic segments, in rats

Author

Hubrecht Institute with UMC, CMM, Circulatory Health, Cancer, Child Health, Brain, CMM Groep Cuppen, Van Der Weide, Robin H., Simonis, Marieke, Hermsen, Roel, Toonen, Pim, Cuppen, Edwin, de Ligt, Joep, Hubrecht Institute with UMC, CMM, Circulatory Health, Cancer, Child Health, Brain, CMM Groep Cuppen, Van Der Weide, Robin H., Simonis, Marieke, Hermsen, Roel, Toonen, Pim, Cuppen, Edwin, and de Ligt, Joep

Published
2016

16. Lack of Major Genome Instability in Tumors of p53 Null Rats

Author

Hermsen, Roel, Toonen, Pim, Kuijk, Ewart, Youssef, Sameh A, Kuiper, Raoul, van Heesch, Sebastiaan, de Bruin, Alain, Cuppen, Edwin, Simonis, Marieke, Hermsen, Roel, Toonen, Pim, Kuijk, Ewart, Youssef, Sameh A, Kuiper, Raoul, van Heesch, Sebastiaan, de Bruin, Alain, Cuppen, Edwin, and Simonis, Marieke

Abstract

Tumorigenesis is often associated with loss of tumor suppressor genes (such as TP53), genomic instability and telomere lengthening. Previously, we generated and characterized a rat p53 knockout model in which the homozygous rats predominantly develop hemangiosarcomas whereas the heterozygous rats mainly develop osteosarcomas. Using genome-wide analyses, we find that the tumors that arise in the heterozygous and homozygous Tp53C273X mutant animals are also different in their genomic instability profiles. While p53 was fully inactivated in both heterozygous and homozygous knockout rats, tumors from homozygous animals show very limited aneuploidy and low degrees of somatic copy number variation as compared to the tumors from heterozygous animals. In addition, complex structural rearrangements such as chromothripsis and breakage-fusion-bridge cycles were never found in tumors from homozygous animals, while these were readily detectable in tumors from heterozygous animals. Finally, we measured telomere length and telomere lengthening pathway activity and found that tumors of homozygous animals have longer telomeres but do not show clear telomerase or alternative lengthening of telomeres (ALT) activity differences as compared to the tumors from heterozygous animals. Taken together, our results demonstrate that host p53 status in this rat p53 knockout model has a large effect on both tumor type and genomic instability characteristics, where full loss of functional p53 is not the main driver of large-scale structural variations. Our results also suggest that chromothripsis primarily occurs under p53 heterozygous rather than p53 null conditions.

Published
2015

17. Genomic landscape of rat strain and substrain variation

Author

Hermsen, Roel, de Ligt, Joep, Spee, Wim, Blokzijl, Francis, Schäfer, Sebastian, Adami, Eleonora, Boymans, Sander, Flink, Stephen, van Boxtel, Ruben, van der Weide, Robin H., Aitman, Tim, Hübner, Norbert, Simonis, Marieke, Tabakoff, Boris, Guryev, Victor, Cuppen, Edwin, Hermsen, Roel, de Ligt, Joep, Spee, Wim, Blokzijl, Francis, Schäfer, Sebastian, Adami, Eleonora, Boymans, Sander, Flink, Stephen, van Boxtel, Ruben, van der Weide, Robin H., Aitman, Tim, Hübner, Norbert, Simonis, Marieke, Tabakoff, Boris, Guryev, Victor, and Cuppen, Edwin

Published
2015

18. Genomic landscape of rat strain and substrain variation

Author

Hermsen, Roel, de Ligt, Joep, Spee, Wim, Blokzijl, Francis, Schäfer, Sebastian, Adami, Eleonora, Boymans, Sander, Flink, Stephen, van Boxtel, Ruben, van der Weide, Robin H., Aitman, Tim, Hübner, Norbert, Simonis, Marieke, Tabakoff, Boris, Guryev, Victor, Cuppen, Edwin, Hermsen, Roel, de Ligt, Joep, Spee, Wim, Blokzijl, Francis, Schäfer, Sebastian, Adami, Eleonora, Boymans, Sander, Flink, Stephen, van Boxtel, Ruben, van der Weide, Robin H., Aitman, Tim, Hübner, Norbert, Simonis, Marieke, Tabakoff, Boris, Guryev, Victor, and Cuppen, Edwin

Published
2015

19. Lack of Major Genome Instability in Tumors of p53 Null Rats

Author

LS Pathobiologie, Tissue Repair, PB TR, Hermsen, Roel, Toonen, Pim, Kuijk, Ewart, Youssef, Sameh A, Kuiper, Raoul, van Heesch, Sebastiaan, de Bruin, Alain, Cuppen, Edwin, Simonis, Marieke, LS Pathobiologie, Tissue Repair, PB TR, Hermsen, Roel, Toonen, Pim, Kuijk, Ewart, Youssef, Sameh A, Kuiper, Raoul, van Heesch, Sebastiaan, de Bruin, Alain, Cuppen, Edwin, and Simonis, Marieke

Published
2015

20. Lack of Major Genome Instability in Tumors of p53 Null Rats

Author

Hermsen, Roel, Toonen, Pim, Kuijk, Ewart, Youssef, Sameh A., Kuiper, Raoul, van Heesch, Sebastiaan, de Bruin, Alain, Cuppen, Edwin, Simonis, Marieke, Hermsen, Roel, Toonen, Pim, Kuijk, Ewart, Youssef, Sameh A., Kuiper, Raoul, van Heesch, Sebastiaan, de Bruin, Alain, Cuppen, Edwin, and Simonis, Marieke

Published
2015

21. Genomic landscape of rat strain and substrain variation

Author

Hermsen, Roel, de Ligt, Joep, Spee, Wim, Blokzijl, Francis, Schäfer, Sebastian, Adami, Eleonora, Boymans, Sander, Flink, Stephen, van Boxtel, Ruben, van der Weide, Robin H, Aitman, Tim, Hübner, Norbert, Simonis, Marieke, Tabakoff, Boris, Guryev, Victor, Cuppen, Edwin, Hermsen, Roel, de Ligt, Joep, Spee, Wim, Blokzijl, Francis, Schäfer, Sebastian, Adami, Eleonora, Boymans, Sander, Flink, Stephen, van Boxtel, Ruben, van der Weide, Robin H, Aitman, Tim, Hübner, Norbert, Simonis, Marieke, Tabakoff, Boris, Guryev, Victor, and Cuppen, Edwin

Abstract

BACKGROUND: Since the completion of the rat reference genome in 2003, whole-genome sequencing data from more than 40 rat strains have become available. These data represent the broad range of strains that are used in rat research including commonly used substrains. Currently, this wealth of information cannot be used to its full extent, because the variety of different variant calling algorithms employed by different groups impairs comparison between strains. In addition, all rat whole genome sequencing studies to date used an outdated reference genome for analysis (RGSC3.4 released in 2004).RESULTS: Here we present a comprehensive, multi-sample and uniformly called set of genetic variants in 40 rat strains, including 19 substrains. We reanalyzed all primary data using a recent version of the rat reference assembly (RGSC5.0 released in 2012) and identified over 12 million genomic variants (SNVs, indels and structural variants) among the 40 strains. 28,318 SNVs are specific to individual substrains, which may be explained by introgression from other unsequenced strains and ongoing evolution by genetic drift. Substrain SNVs may have a larger predicted functional impact compared to older shared SNVs.CONCLUSIONS: In summary we present a comprehensive catalog of uniformly analyzed genetic variants among 40 widely used rat inbred strains based on the RGSC5.0 assembly. This represents a valuable resource, which will facilitate rat functional genomic research. In line with previous observations, our genome-wide analyses do not show evidence for contribution of multiple ancestral founder rat subspecies to the currently used rat inbred strains, as is the case for mouse. In addition, we find that the degree of substrain variation is highly variable between strains, which is of importance for the correct interpretation of experimental data from different labs.

Published
2015

22. Lack of Major Genome Instability in Tumors of p53 Null Rats

Author

Hermsen, Roel, Toonen, Pim, Kuijk, Ewart, Youssef, Sameh A, Kuiper, Raoul, van Heesch, Sebastiaan, de Bruin, Alain, Cuppen, Edwin, Simonis, Marieke, Hermsen, Roel, Toonen, Pim, Kuijk, Ewart, Youssef, Sameh A, Kuiper, Raoul, van Heesch, Sebastiaan, de Bruin, Alain, Cuppen, Edwin, and Simonis, Marieke

Abstract

Tumorigenesis is often associated with loss of tumor suppressor genes (such as TP53), genomic instability and telomere lengthening. Previously, we generated and characterized a rat p53 knockout model in which the homozygous rats predominantly develop hemangiosarcomas whereas the heterozygous rats mainly develop osteosarcomas. Using genome-wide analyses, we find that the tumors that arise in the heterozygous and homozygous Tp53C273X mutant animals are also different in their genomic instability profiles. While p53 was fully inactivated in both heterozygous and homozygous knockout rats, tumors from homozygous animals show very limited aneuploidy and low degrees of somatic copy number variation as compared to the tumors from heterozygous animals. In addition, complex structural rearrangements such as chromothripsis and breakage-fusion-bridge cycles were never found in tumors from homozygous animals, while these were readily detectable in tumors from heterozygous animals. Finally, we measured telomere length and telomere lengthening pathway activity and found that tumors of homozygous animals have longer telomeres but do not show clear telomerase or alternative lengthening of telomeres (ALT) activity differences as compared to the tumors from heterozygous animals. Taken together, our results demonstrate that host p53 status in this rat p53 knockout model has a large effect on both tumor type and genomic instability characteristics, where full loss of functional p53 is not the main driver of large-scale structural variations. Our results also suggest that chromothripsis primarily occurs under p53 heterozygous rather than p53 null conditions.

Published
2015

23. Lack of Major Genome Instability in Tumors of p53 Null Rats

Author

Hermsen, Roel, Toonen, Pim, Kuijk, Ewart, Youssef, Sameh A., Kuiper, Raoul, van Heesch, Sebastiaan, de Bruin, Alain, Cuppen, Edwin, Simonis, Marieke, Hermsen, Roel, Toonen, Pim, Kuijk, Ewart, Youssef, Sameh A., Kuiper, Raoul, van Heesch, Sebastiaan, de Bruin, Alain, Cuppen, Edwin, and Simonis, Marieke

Published
2015

24. Genomic landscape of rat strain and substrain variation

Author

Hermsen, Roel, de Ligt, Joep, Spee, Wim, Blokzijl, Francis, Schäfer, Sebastian, Adami, Eleonora, Boymans, Sander, Flink, Stephen, van Boxtel, Ruben, van der Weide, Robin H., Aitman, Tim, Hübner, Norbert, Simonis, Marieke, Tabakoff, Boris, Guryev, Victor, Cuppen, Edwin, Hermsen, Roel, de Ligt, Joep, Spee, Wim, Blokzijl, Francis, Schäfer, Sebastian, Adami, Eleonora, Boymans, Sander, Flink, Stephen, van Boxtel, Ruben, van der Weide, Robin H., Aitman, Tim, Hübner, Norbert, Simonis, Marieke, Tabakoff, Boris, Guryev, Victor, and Cuppen, Edwin

Published
2015

25. Lack of Major Genome Instability in Tumors of p53 Null Rats

Author

LS Pathobiologie, Tissue Repair, PB TR, Hermsen, Roel, Toonen, Pim, Kuijk, Ewart, Youssef, Sameh A, Kuiper, Raoul, van Heesch, Sebastiaan, de Bruin, Alain, Cuppen, Edwin, Simonis, Marieke, LS Pathobiologie, Tissue Repair, PB TR, Hermsen, Roel, Toonen, Pim, Kuijk, Ewart, Youssef, Sameh A, Kuiper, Raoul, van Heesch, Sebastiaan, de Bruin, Alain, Cuppen, Edwin, and Simonis, Marieke

Published
2015

26. Lack of Major Genome Instability in Tumors of p53 Null Rats

Author

CMM Groep Cuppen, CMM Sectie Genomics and Bioinformatics, Cancer, Hubrecht Institute with UMC, Child Health, Hermsen, Roel, Toonen, Pim, Kuijk, Ewart, Youssef, Sameh A., Kuiper, Raoul, van Heesch, Sebastiaan, de Bruin, Alain, Cuppen, Edwin, Simonis, Marieke, CMM Groep Cuppen, CMM Sectie Genomics and Bioinformatics, Cancer, Hubrecht Institute with UMC, Child Health, Hermsen, Roel, Toonen, Pim, Kuijk, Ewart, Youssef, Sameh A., Kuiper, Raoul, van Heesch, Sebastiaan, de Bruin, Alain, Cuppen, Edwin, and Simonis, Marieke

Published
2015

27. Genomic landscape of rat strain and substrain variation

Author

CMM Sectie Genomics and Bioinformatics, Cancer, Hubrecht Institute with UMC, Child Health, Hermsen, Roel, de Ligt, Joep, Spee, Wim, Blokzijl, Francis, Schäfer, Sebastian, Adami, Eleonora, Boymans, Sander, Flink, Stephen, van Boxtel, Ruben, van der Weide, Robin H., Aitman, Tim, Hübner, Norbert, Simonis, Marieke, Tabakoff, Boris, Guryev, Victor, Cuppen, Edwin, CMM Sectie Genomics and Bioinformatics, Cancer, Hubrecht Institute with UMC, Child Health, Hermsen, Roel, de Ligt, Joep, Spee, Wim, Blokzijl, Francis, Schäfer, Sebastian, Adami, Eleonora, Boymans, Sander, Flink, Stephen, van Boxtel, Ruben, van der Weide, Robin H., Aitman, Tim, Hübner, Norbert, Simonis, Marieke, Tabakoff, Boris, Guryev, Victor, and Cuppen, Edwin

Published
2015

28. Genomic landscape of rat strain and substrain variation

Author

Hermsen, Roel, de Ligt, Joep, Spee, Wim, Blokzijl, Francis, Schäfer, Sebastian, Adami, Eleonora, Boymans, Sander, Flink, Stephen, van Boxtel, Ruben, van der Weide, Robin H, Aitman, Tim, Hübner, Norbert, Simonis, Marieke, Tabakoff, Boris, Guryev, Victor, Cuppen, Edwin, Hermsen, Roel, de Ligt, Joep, Spee, Wim, Blokzijl, Francis, Schäfer, Sebastian, Adami, Eleonora, Boymans, Sander, Flink, Stephen, van Boxtel, Ruben, van der Weide, Robin H, Aitman, Tim, Hübner, Norbert, Simonis, Marieke, Tabakoff, Boris, Guryev, Victor, and Cuppen, Edwin

Abstract

BACKGROUND: Since the completion of the rat reference genome in 2003, whole-genome sequencing data from more than 40 rat strains have become available. These data represent the broad range of strains that are used in rat research including commonly used substrains. Currently, this wealth of information cannot be used to its full extent, because the variety of different variant calling algorithms employed by different groups impairs comparison between strains. In addition, all rat whole genome sequencing studies to date used an outdated reference genome for analysis (RGSC3.4 released in 2004).RESULTS: Here we present a comprehensive, multi-sample and uniformly called set of genetic variants in 40 rat strains, including 19 substrains. We reanalyzed all primary data using a recent version of the rat reference assembly (RGSC5.0 released in 2012) and identified over 12 million genomic variants (SNVs, indels and structural variants) among the 40 strains. 28,318 SNVs are specific to individual substrains, which may be explained by introgression from other unsequenced strains and ongoing evolution by genetic drift. Substrain SNVs may have a larger predicted functional impact compared to older shared SNVs.CONCLUSIONS: In summary we present a comprehensive catalog of uniformly analyzed genetic variants among 40 widely used rat inbred strains based on the RGSC5.0 assembly. This represents a valuable resource, which will facilitate rat functional genomic research. In line with previous observations, our genome-wide analyses do not show evidence for contribution of multiple ancestral founder rat subspecies to the currently used rat inbred strains, as is the case for mouse. In addition, we find that the degree of substrain variation is highly variable between strains, which is of importance for the correct interpretation of experimental data from different labs.

Published
2015

29. Lack of Major Genome Instability in Tumors of p53 Null Rats

Author

Hermsen, Roel, Toonen, Pim, Kuijk, Ewart, Youssef, Sameh A, Kuiper, Raoul, van Heesch, Sebastiaan, de Bruin, Alain, Cuppen, Edwin, Simonis, Marieke, Hermsen, Roel, Toonen, Pim, Kuijk, Ewart, Youssef, Sameh A, Kuiper, Raoul, van Heesch, Sebastiaan, de Bruin, Alain, Cuppen, Edwin, and Simonis, Marieke

Abstract

Tumorigenesis is often associated with loss of tumor suppressor genes (such as TP53), genomic instability and telomere lengthening. Previously, we generated and characterized a rat p53 knockout model in which the homozygous rats predominantly develop hemangiosarcomas whereas the heterozygous rats mainly develop osteosarcomas. Using genome-wide analyses, we find that the tumors that arise in the heterozygous and homozygous Tp53C273X mutant animals are also different in their genomic instability profiles. While p53 was fully inactivated in both heterozygous and homozygous knockout rats, tumors from homozygous animals show very limited aneuploidy and low degrees of somatic copy number variation as compared to the tumors from heterozygous animals. In addition, complex structural rearrangements such as chromothripsis and breakage-fusion-bridge cycles were never found in tumors from homozygous animals, while these were readily detectable in tumors from heterozygous animals. Finally, we measured telomere length and telomere lengthening pathway activity and found that tumors of homozygous animals have longer telomeres but do not show clear telomerase or alternative lengthening of telomeres (ALT) activity differences as compared to the tumors from heterozygous animals. Taken together, our results demonstrate that host p53 status in this rat p53 knockout model has a large effect on both tumor type and genomic instability characteristics, where full loss of functional p53 is not the main driver of large-scale structural variations. Our results also suggest that chromothripsis primarily occurs under p53 heterozygous rather than p53 null conditions.

Published
2015

30. Extensive localization of long noncoding RNAs to the cytosol and mono- and polyribosomal complexes

Author

van Heesch, Sebastiaan, van Iterson, Maarten, Jacobi, Jetse, Boymans, Sander, Essers, Paul B, de Bruijn, Ewart, Hao, Wensi, MacInnes, Alyson W, Cuppen, Edwin, Simonis, Marieke, van Heesch, Sebastiaan, van Iterson, Maarten, Jacobi, Jetse, Boymans, Sander, Essers, Paul B, de Bruijn, Ewart, Hao, Wensi, MacInnes, Alyson W, Cuppen, Edwin, and Simonis, Marieke

Abstract

BACKGROUND: Long noncoding RNAs (lncRNAs) form an abundant class of transcripts, but the function of the majority of them remains elusive. While it has been shown that some lncRNAs are bound by ribosomes, it has also been convincingly demonstrated that these transcripts do not code for proteins. To obtain a comprehensive understanding of the extent to which lncRNAs bind ribosomes, we performed systematic RNA sequencing on ribosome-associated RNA pools obtained through ribosomal fractionation and compared the RNA content with nuclear and (non-ribosome bound) cytosolic RNA pools.RESULTS: The RNA composition of the subcellular fractions differs significantly from each other, but lncRNAs are found in all locations. A subset of specific lncRNAs is enriched in the nucleus but surprisingly the majority is enriched in the cytosol and in ribosomal fractions. The ribosomal enriched lncRNAs include H19 and TUG1.CONCLUSIONS: Most studies on lncRNAs have focused on the regulatory function of these transcripts in the nucleus. We demonstrate that only a minority of all lncRNAs are nuclear enriched. Our findings suggest that many lncRNAs may have a function in cytoplasmic processes, and in particular in ribosome complexes.

Published
2014

31. Genomic and Functional Overlap between Somatic and Germline Chromosomal Rearrangements

Author

van Heesch, Sebastiaan, Simonis, Marieke, van Roosmalen, Markus J, Pillalamarri, Vamsee, Brand, Harrison, Kuijk, Ewart W, de Luca, Kim L, Lansu, Nico, Braat, A Koen, Menelaou, Androniki, Hao, Wensi, Korving, Jeroen, Snijder, Simone, van der Veken, Lars T, Hochstenbach, Ron, Knegt, Alida C, Duran, Karen, Renkens, Ivo, Alekozai, Najla, Jager, Myrthe, Vergult, Sarah, Menten, Björn, de Bruijn, Ewart, Boymans, Sander, Ippel, Elly, van Binsbergen, Ellen, Talkowski, Michael E, Lichtenbelt, Klaske, Cuppen, Edwin, Kloosterman, Wigard P, van Heesch, Sebastiaan, Simonis, Marieke, van Roosmalen, Markus J, Pillalamarri, Vamsee, Brand, Harrison, Kuijk, Ewart W, de Luca, Kim L, Lansu, Nico, Braat, A Koen, Menelaou, Androniki, Hao, Wensi, Korving, Jeroen, Snijder, Simone, van der Veken, Lars T, Hochstenbach, Ron, Knegt, Alida C, Duran, Karen, Renkens, Ivo, Alekozai, Najla, Jager, Myrthe, Vergult, Sarah, Menten, Björn, de Bruijn, Ewart, Boymans, Sander, Ippel, Elly, van Binsbergen, Ellen, Talkowski, Michael E, Lichtenbelt, Klaske, Cuppen, Edwin, and Kloosterman, Wigard P

Abstract

Genomic rearrangements are a common cause of human congenital abnormalities. However, their origin and consequences are poorly understood. We performed molecular analysis of two patients with congenital disease who carried de novo genomic rearrangements. We found that the rearrangements in both patients hit genes that are recurrently rearranged in cancer (ETV1, FOXP1, and microRNA cluster C19MC) and drive formation of fusion genes similar to those described in cancer. Subsequent analysis of a large set of 552 de novo germline genomic rearrangements underlying congenital disorders revealed enrichment for genes rearranged in cancer and overlap with somatic cancer breakpoints. Breakpoints of common (inherited) germline structural variations also overlap with cancer breakpoints but are depleted for cancer genes. We propose that the same genomic positions are prone to genomic rearrangements in germline and soma but that timing and context of breakage determines whether developmental defects or cancer are promoted.

Published
2014

32. Extensive localization of long noncoding RNAs to the cytosol and mono- and polyribosomal complexes

Author

van Heesch, Sebastiaan, van Iterson, Maarten, Jacobi, Jetse, Boymans, Sander, Essers, Paul B, de Bruijn, Ewart, Hao, Wensi, MacInnes, Alyson W, Cuppen, Edwin, Simonis, Marieke, van Heesch, Sebastiaan, van Iterson, Maarten, Jacobi, Jetse, Boymans, Sander, Essers, Paul B, de Bruijn, Ewart, Hao, Wensi, MacInnes, Alyson W, Cuppen, Edwin, and Simonis, Marieke

Abstract

BACKGROUND: Long noncoding RNAs (lncRNAs) form an abundant class of transcripts, but the function of the majority of them remains elusive. While it has been shown that some lncRNAs are bound by ribosomes, it has also been convincingly demonstrated that these transcripts do not code for proteins. To obtain a comprehensive understanding of the extent to which lncRNAs bind ribosomes, we performed systematic RNA sequencing on ribosome-associated RNA pools obtained through ribosomal fractionation and compared the RNA content with nuclear and (non-ribosome bound) cytosolic RNA pools.RESULTS: The RNA composition of the subcellular fractions differs significantly from each other, but lncRNAs are found in all locations. A subset of specific lncRNAs is enriched in the nucleus but surprisingly the majority is enriched in the cytosol and in ribosomal fractions. The ribosomal enriched lncRNAs include H19 and TUG1.CONCLUSIONS: Most studies on lncRNAs have focused on the regulatory function of these transcripts in the nucleus. We demonstrate that only a minority of all lncRNAs are nuclear enriched. Our findings suggest that many lncRNAs may have a function in cytoplasmic processes, and in particular in ribosome complexes.

Published
2014

33. Genomic and Functional Overlap between Somatic and Germline Chromosomal Rearrangements

Author

van Heesch, Sebastiaan, Simonis, Marieke, van Roosmalen, Markus J, Pillalamarri, Vamsee, Brand, Harrison, Kuijk, Ewart W, de Luca, Kim L, Lansu, Nico, Braat, A Koen, Menelaou, Androniki, Hao, Wensi, Korving, Jeroen, Snijder, Simone, van der Veken, Lars T, Hochstenbach, Ron, Knegt, Alida C, Duran, Karen, Renkens, Ivo, Alekozai, Najla, Jager, Myrthe, Vergult, Sarah, Menten, Björn, de Bruijn, Ewart, Boymans, Sander, Ippel, Elly, van Binsbergen, Ellen, Talkowski, Michael E, Lichtenbelt, Klaske, Cuppen, Edwin, Kloosterman, Wigard P, van Heesch, Sebastiaan, Simonis, Marieke, van Roosmalen, Markus J, Pillalamarri, Vamsee, Brand, Harrison, Kuijk, Ewart W, de Luca, Kim L, Lansu, Nico, Braat, A Koen, Menelaou, Androniki, Hao, Wensi, Korving, Jeroen, Snijder, Simone, van der Veken, Lars T, Hochstenbach, Ron, Knegt, Alida C, Duran, Karen, Renkens, Ivo, Alekozai, Najla, Jager, Myrthe, Vergult, Sarah, Menten, Björn, de Bruijn, Ewart, Boymans, Sander, Ippel, Elly, van Binsbergen, Ellen, Talkowski, Michael E, Lichtenbelt, Klaske, Cuppen, Edwin, and Kloosterman, Wigard P

Abstract

Genomic rearrangements are a common cause of human congenital abnormalities. However, their origin and consequences are poorly understood. We performed molecular analysis of two patients with congenital disease who carried de novo genomic rearrangements. We found that the rearrangements in both patients hit genes that are recurrently rearranged in cancer (ETV1, FOXP1, and microRNA cluster C19MC) and drive formation of fusion genes similar to those described in cancer. Subsequent analysis of a large set of 552 de novo germline genomic rearrangements underlying congenital disorders revealed enrichment for genes rearranged in cancer and overlap with somatic cancer breakpoints. Breakpoints of common (inherited) germline structural variations also overlap with cancer breakpoints but are depleted for cancer genes. We propose that the same genomic positions are prone to genomic rearrangements in germline and soma but that timing and context of breakage determines whether developmental defects or cancer are promoted.

Published
2014

34. Justice and the Human Alarm System: The Impact of Exclamation Points and Flashing Lights on the Justice Judgment Process

Author

Bos, Kees van den, Ham, Jaap, Lind, E. Allan, Simonis, Marieke, Essen, Wiljo J. van, Rijpkema, Mark, Bos, Kees van den, Ham, Jaap, Lind, E. Allan, Simonis, Marieke, Essen, Wiljo J. van, and Rijpkema, Mark

Abstract

Extending theory within the justice domain and work on the human alarm system, the current paper argues that the process by which justice judgments are formed may be influenced reliably by the activation of psychological systems that people use to detect and handle alarming situations. Building on this analysis, it is further proposed that if this line of reasoning is true then presenting alarm-related stimuli, such as exclamation points and flashing lights, to people should lead to more extreme judgments about subsequent justice-related events than not presenting these alarming stimuli. Findings collected using different experimental paradigms provide evidence supporting these predictions both inside and outside the psychology lab. Implications for the social psychology of justice and the human alarm system literature are discussed.

Published
2011

Catalog

Books, media, physical & digital resources
See catalog results