Search

Your search keyword '"Wong, Christine E."' showing total 20 results
Start Over Author "Wong, Christine E."
20 results on '"Wong, Christine E."'

1. Lgr6 is a stem cell marker in mouse skin squamous cell carcinoma

Author

Huang, Phillips Y, Kandyba, Eve, Jabouille, Arnaud, Sjolund, Jonas, Kumar, Atul, Halliwill, Kyle, McCreery, Melissa, DelRosario, Reyno, Kang, Hio Chung, Wong, Christine E, Seibler, Jost, Beuger, Vincent, Pellegrino, Maurizio, Sciambi, Adam, Eastburn, Dennis J, and Balmain, Allan

Subjects
Stem Cell Research - Nonembryonic - Non-Human, Cancer, Stem Cell Research, Animals, Carcinoma, Squamous Cell, Cell Line, Transformed, Epidermis, Gene Expression Regulation, Neoplastic, Humans, Keratinocytes, Mice, Mice, Transgenic, Neoplastic Stem Cells, RNA, Small Interfering, Receptors, G-Protein-Coupled, Signal Transduction, Skin Neoplasms, Thrombospondins, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

The G-protein-coupled receptors LGR4, LGR5 and LGR6 are Wnt signaling mediators, but their functions in squamous cell carcinoma (SCC) are unclear. Using lineage tracing in Lgr5-EGFP-CreERT2/Rosa26-Tomato and Lgr6-EGFP-CreERT2/Rosa26-Tomato reporter mice, we demonstrate that Lgr6, but not Lgr5, acts as an epithelial stem cell marker in SCCs in vivo. We identify, by single-molecule in situ hybridization and cell sorting, rare cells positive for Lgr6 expression in immortalized keratinocytes and show that their frequency increases in advanced SCCs. Lgr6 expression is enriched in cells with stem cell characteristics, and Lgr6 downregulation in vivo causes increased epidermal proliferation with expanded lineage tracing from epidermal stem cells positive for Lgr6 expression. Surprisingly, mice with germline knockout of Lgr6 are predisposed to SCC development, through a mechanism that includes compensatory upregulation of Lgr5. These data provide a model for human patients with germline loss-of-function mutations in Wnt pathway genes, including RSPO1 or LGR4, who show increased susceptibility to squamous tumor development.

Published
2017

2. Gene Expression Architecture of Mouse Dorsal and Tail Skin Reveals Functional Differences in Inflammation and Cancer.

Author

Quigley, David A, Kandyba, Eve, Huang, Phillips, Halliwill, Kyle D, Sjölund, Jonas, Pelorosso, Facundo, Wong, Christine E, Hirst, Gillian L, Wu, Di, Delrosario, Reyno, Kumar, Atul, and Balmain, Allan

Subjects
Germ Cells, Skin, Animals, Mice, Skin Neoplasms, Disease Progression, Genetic Predisposition to Disease, Inflammation, Signal Transduction, Gene Expression, Polymorphism, Genetic, Quantitative Trait Loci, Gene Regulatory Networks, Carcinogenesis, Genetics, Cancer, Biotechnology, Stem Cell Research - Nonembryonic - Non-Human, Stem Cell Research, Aetiology, 2.1 Biological and endogenous factors, Inflammatory and immune system, Biochemistry and Cell Biology, Medical Physiology
Abstract

Inherited germline polymorphisms can cause gene expression levels in normal tissues to differ substantially between individuals. We present an analysis of the genetic architecture of normal adult skin from 470 genetically unique mice, demonstrating the effect of germline variants, skin tissue location, and perturbation by exogenous inflammation or tumorigenesis on gene signaling pathways. Gene networks related to specific cell types and signaling pathways, including sonic hedgehog (Shh), Wnt, Lgr family stem cell markers, and keratins, differed at these tissue sites, suggesting mechanisms for the differential susceptibility of dorsal and tail skin to development of skin diseases and tumorigenesis. The Pten tumor suppressor gene network is rewired in premalignant tumors compared to normal tissue, but this response to perturbation is lost during malignant progression. We present a software package for expression quantitative trait loci (eQTL) network analysis and demonstrate how network analysis of whole tissues provides insights into interactions between cell compartments and signaling molecules.

Published
2016

3. Inflammation and Hras signaling control epithelial–mesenchymal transition during skin tumor progression

Author

Wong, Christine E, Yu, Jennifer S, Quigley, David A, To, Minh D, Jen, Kuang-Yu, Huang, Phillips Y, Del Rosario, Reyno, and Balmain, Allan

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Genetics, Cancer, 2.1 Biological and endogenous factors, Aetiology, Animals, Carcinoma, Squamous Cell, Cyclin-Dependent Kinase Inhibitor Proteins, Epithelial-Mesenchymal Transition, ErbB Receptors, Gene Dosage, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Genetic Markers, Inflammation, Mice, Mutation, Proto-Oncogene Proteins p21(ras), Signal Transduction, Skin Neoplasms, EMT, Hras, inflammation, skin carcinogenesis, stem cells, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences, Psychology
Abstract

Epithelial-mesenchymal transition (EMT) is thought to be an important, possibly essential, component of the process of tumor dissemination and metastasis. About 20%-30% of Hras mutant mouse skin carcinomas induced by chemical initiation/promotion protocols have undergone EMT. Reduced exposure to TPA-induced chronic inflammation causes a dramatic reduction in classical papillomas and squamous cell carcinomas (SCCs), but the mice still develop highly invasive carcinomas with EMT properties, reduced levels of Hras and Egfr signaling, and frequent Ink4/Arf deletions. Deletion of Hras from the mouse germline also leads to a strong reduction in squamous tumor development, but tumors now acquire activating Kras mutations and exhibit more aggressive metastatic properties. We propose that invasive carcinomas can arise by different genetic and biological routes dependent on exposure to chronic inflammation and possibly from different target cell populations within the skin. Our data have implications for the use of inhibitors of inflammation or of Ras/Egfr pathway signaling for prevention or treatment of invasive cancers.

Published
2013

7. Neural crest-derived cells with stem cell features can be traced back to multiple lineages in the adult skin

Author

Wong, Christine E., Paratore, Christian, Dours-Zimmermann, Maria T., Rochat, Ariane, Pietri, Thomas, Suter, Ueli, Zimmermann, Dieter R., Dufour, Sylvie, Thiery, Jean Paul, Meijer, Dies, Beermann, Friedrich, Barrandon, Yann, and Sommer, Lukas

Subjects
Neural crest -- Research, Skin -- Research, Stem cells, Stem cell research, Biological sciences
Abstract

Given their accessibility, multipotent skin-derived cells might be useful for future cell replacement therapies. We describe the isolation of multipotent stem cell-like cells from the adult trunk skin of mice and humans that express the neural crest stem cell markers p75 and Sox10 and display extensive self-renewal capacity in sphere cultures. To determine the origin of these cells, we genetically mapped the fate of neural crest cells in face and trunk skin of mouse. In whisker follicles of the face, many mesenchymal structures are neural crest derived and appear to contain cells with sphere-forming potential. In the trunk skin, however, sphere-forming neural crest-derived cells are restricted to the glial and melanocyte lineages. Thus, self-renewing cells in the adult skin can be obtained from several neural crest derivatives, and these are of distinct nature in face and trunk skin. These findings are relevant for the design of therapeutic strategies because the potential of stem and progenitor cells in vivo likely depends on their nature and origin.

Published
2006

8. Human infection with a triple-reassortant swine influenza A (H1N1) virus containing the hemagglutinin and neuraminidase genes of seasonal influenza virus

Author

Bastien, Nathalie, Antonishyn, Nick A., Brandt, Ken, Wong, Christine E., Chokani, Khami, Vegh, Niki, Horsman, Greg B., Tyler, Shaun, Graham, Morag R., Plummer, Frank A., Levett, Paul N., and Li, Yan

Subjects
Swine influenza -- Development and progression, Swine influenza -- Genetic aspects, Swine influenza -- Research, Agglutinins -- Genetic aspects, Agglutinins -- Research, Polymerase chain reaction -- Usage, Polymerase chain reaction -- Research, Health
Published
2010

9. Multi-region proteome analysis quantifies spatial heterogeneity of prostate tissue biomarkers

Author

Guo, Tiannan, primary, Li, Li, additional, Zhong, Qing, additional, Rupp, Niels J, additional, Charmpi, Konstantina, additional, Wong, Christine E, additional, Wagner, Ulrich, additional, Rueschoff, Jan H, additional, Jochum, Wolfram, additional, Fankhauser, Christian Daniel, additional, Saba, Karim, additional, Poyet, Cedric, additional, Wild, Peter J, additional, Aebersold, Ruedi, additional, and Beyer, Andreas, additional

Published
2018
Full Text
View/download PDF

10. Targeted next-generation-sequencing for reliable detection of targetable rearrangements in lung adenocarcinoma—a single center retrospective study

Author

Velizheva, Nadezda P., primary, Rechsteiner, Markus P., additional, Valtcheva, Nadejda, additional, Freiberger, Sandra N., additional, Wong, Christine E., additional, Vrugt, Bart, additional, Zhong, Qing, additional, Wagner, Ulrich, additional, Moch, Holger, additional, Hillinger, Sven, additional, Schmitt-Opitz, Isabelle, additional, Soltermann, Alex, additional, Wild, Peter J., additional, and Tischler, Verena, additional

Published
2018
Full Text
View/download PDF

11. Multi-region proteome analysis quantifies spatial heterogeneity of prostate tissue biomarkers

Author

Guo, Tiannan, Li, Li, Zhong, Qing, Rupp, Niels J., Charmpi, Konstantina, Wong, Christine E., Wagner, Ulrich, Rueschoff, Jan H., Jochum, Wolfram, Fankhauser, Christian Daniel, Saba, Karim, Poyet, Cedric, Wild, Peter J., Aebersold, Ruedi, Beyer, Andreas, Guo, Tiannan, Li, Li, Zhong, Qing, Rupp, Niels J., Charmpi, Konstantina, Wong, Christine E., Wagner, Ulrich, Rueschoff, Jan H., Jochum, Wolfram, Fankhauser, Christian Daniel, Saba, Karim, Poyet, Cedric, Wild, Peter J., Aebersold, Ruedi, and Beyer, Andreas

Abstract

It remains unclear to what extent tumor heterogeneity impacts on protein biomarker discovery. Here, we quantified proteome intra-tissue heterogeneity (ITH) based on a multi-region analysis of prostate tissues using pressure cycling technology and Sequential Windowed Acquisition of all THeoretical fragment ion mass spectrometry. We quantified 6,873 proteins and analyzed the ITH of 3,700 proteins. The level of ITH varied depending on proteins and tissue types. Benign tissues exhibited more complex ITH patterns than malignant tissues. Spatial variability of 10 prostate biomarkers was validated by immunohistochemistry in an independent cohort (n = 83) using tissue microarrays. Prostate-specific antigen was preferentially variable in benign prostatic hyperplasia, whereas growth/differentiation factor 15 substantially varied in prostate adenocarcinomas. Furthermore, we found that DNA repair pathways exhibited a high degree of variability in tumorous tissues, which may contribute to the genetic heterogeneity of tumors. This study conceptually adds a new perspective to protein biomarker discovery: it suggests that recent technological progress should be exploited to quantify and account for spatial proteome variation to complement biomarker identification and utilization.

Published
2018

12. Targeted next-generation-sequencing for reliable detection of targetable rearrangements in lung adenocarcinoma-a single center retrospective study

Author

Velizheva, Nadezda P, Rechsteiner, Markus P, Valtcheva, Nadejda, Freiberger, Sandra N, Wong, Christine E, Vrugt, Bart, Zhong, Qing, Wagner, Ulrich, Moch, Holger, Hillinger, Sven, Schmitt-Opitz, Isabelle, Soltermann, Alex, Wild, Peter J, Tischler, Verena, Velizheva, Nadezda P, Rechsteiner, Markus P, Valtcheva, Nadejda, Freiberger, Sandra N, Wong, Christine E, Vrugt, Bart, Zhong, Qing, Wagner, Ulrich, Moch, Holger, Hillinger, Sven, Schmitt-Opitz, Isabelle, Soltermann, Alex, Wild, Peter J, and Tischler, Verena

Abstract

Oncogenic rearrangements leading to targetable gene fusions are well-established cancer driver events in lung adenocarcinoma. Accurate and reliable detection of these gene fusions is crucial to select the appropriate targeted therapy for each patient. We compared the targeted next-generation-sequencing Oncomine Focus Assay (OFA; Thermo Fisher Scientific) with conventional ALK FISH and anti-Alk immunohistochemistry in a cohort of 52 lung adenocarcinomas (10 ALK rearranged, 18 non-ALK rearranged, and 24 untested cases). We found a sensitivity and specificity of 100% for detection of ALK rearrangements using the OFA panel. In addition, targeted next generation sequencing allowed us to analyze a set of 23 driver genes in a single assay. Besides EML4-ALK (11/52 cases), we detected EZR-ROS1 (1/52 cases), KIF5B-RET (1/52 cases) and MET-MET (4/52 cases) fusions. All EML4-ALK, EZR-ROS1 and KIF5B-RET fusions were confirmed by multiplexed targeted next generation sequencing assay (Oncomine Solid Tumor Fusion Transcript Kit, Thermo Fisher Scientific). All cases with EML4-ALK rearrangement were confirmed by Alk immunohistochemistry and all but one by ALK FISH. In our experience, targeted next-generation sequencing is a reliable and timesaving tool for multiplexed detection of targetable rearrangements. Therefore, targeted next-generation sequencing represents an efficient alternative to time-consuming single target assays currently used in molecular pathology.

Published
2018

13. Multi-region proteome analysis quantifies spatial heterogeneity of prostate tissue biomarkers

Author

Guo, Tiannan; https://orcid.org/0000-0003-3869-7651, Li, Li, Zhong, Qing; https://orcid.org/0000-0002-5340-301X, Rupp, Niels J, Charmpi, Konstantina, Wong, Christine E, Wagner, Ulrich; https://orcid.org/0000-0002-1751-5866, Rueschoff, Jan H, Jochum, Wolfram; https://orcid.org/0000-0001-6170-2020, Fankhauser, Christian Daniel; https://orcid.org/0000-0002-4073-5488, Saba, Karim; https://orcid.org/0000-0002-1172-8123, Poyet, Cedric; https://orcid.org/0000-0002-3648-6941, Wild, Peter J; https://orcid.org/0000-0002-1017-3744, Aebersold, Ruedi; https://orcid.org/0000-0002-9576-3267, Beyer, Andreas; https://orcid.org/0000-0002-3891-2123, Guo, Tiannan; https://orcid.org/0000-0003-3869-7651, Li, Li, Zhong, Qing; https://orcid.org/0000-0002-5340-301X, Rupp, Niels J, Charmpi, Konstantina, Wong, Christine E, Wagner, Ulrich; https://orcid.org/0000-0002-1751-5866, Rueschoff, Jan H, Jochum, Wolfram; https://orcid.org/0000-0001-6170-2020, Fankhauser, Christian Daniel; https://orcid.org/0000-0002-4073-5488, Saba, Karim; https://orcid.org/0000-0002-1172-8123, Poyet, Cedric; https://orcid.org/0000-0002-3648-6941, Wild, Peter J; https://orcid.org/0000-0002-1017-3744, Aebersold, Ruedi; https://orcid.org/0000-0002-9576-3267, and Beyer, Andreas; https://orcid.org/0000-0002-3891-2123

Abstract

It remains unclear to what extent tumor heterogeneity impacts on protein biomarker discovery. Here, we quantified proteome intra-tissue heterogeneity (ITH) based on a multi-region analysis of prostate tissues using pressure cycling technology and Sequential Windowed Acquisition of all THeoretical fragment ion mass spectrometry. We quantified 6,873 proteins and analyzed the ITH of 3,700 proteins. The level of ITH varied depending on proteins and tissue types. Benign tissues exhibited more complex ITH patterns than malignant tissues. Spatial variability of 10 prostate biomarkers was validated by immunohistochemistry in an independent cohort (n = 83) using tissue microarrays. Prostate-specific antigen was preferentially variable in benign prostatic hyperplasia, whereas growth/differentiation factor 15 substantially varied in prostate adenocarcinomas. Furthermore, we found that DNA repair pathways exhibited a high degree of variability in tumorous tissues, which may contribute to the genetic heterogeneity of tumors. This study conceptually adds a new perspective to protein biomarker discovery: it suggests that recent technological progress should be exploited to quantify and account for spatial proteome variation to complement biomarker identification and utilization.

Published
2018

14. Targeted next-generation-sequencing for reliable detection of targetable rearrangements in lung adenocarcinoma - a single center retrospective study

Author

Velizheva, Nadezda P., Rechsteiner, Markus, Valtcheva, Nadejda, Freiberger, Sandra N., Wong, Christine E., Vrugt, Bart, Zhong, Qing, Wagner, Ulrich, Moch, Holger, Hillinger, Sven, Opitz, Isabelle, Soltermann, Alex, Wild, Peter Johannes, Tischler, Verena, Velizheva, Nadezda P., Rechsteiner, Markus, Valtcheva, Nadejda, Freiberger, Sandra N., Wong, Christine E., Vrugt, Bart, Zhong, Qing, Wagner, Ulrich, Moch, Holger, Hillinger, Sven, Opitz, Isabelle, Soltermann, Alex, Wild, Peter Johannes, and Tischler, Verena

Abstract

Oncogenic rearrangements leading to targetable gene fusions are well-established cancer driver events in lung adenocarcinoma. Accurate and reliable detection of these gene fusions is crucial to select the appropriate targeted therapy for each patient. We compared the targeted next-generation-sequencing Oncomine Focus Assay (OFA; Thermo Fisher Scientific) with conventional ALK FISH and anti-Alk immunohistochemistry in a cohort of 52 lung adenocarcinomas (10 ALK rearranged, 18 non-ALK rearranged, and 24 untested cases). We found a sensitivity and specificity of 100% for detection of ALK rearrangements using the OFA panel. In addition, targeted next generation sequencing allowed us to analyze a set of 23 driver genes in a single assay. Besides EML4-ALK (11/52 cases), we detected EZR-ROS1 (1/52 cases), KIF5B-RET (1/52 cases) and MET-MET (4/52 cases) fusions. All EML4-ALK, EZR-ROS1 and KIF5B-RET fusions were confirmed by multiplexed targeted next generation sequencing assay (Oncomine Solid Tumor Fusion Transcript Kit, Thermo Fisher Scientific). All cases with EML4-ALK rearrangement were confirmed by Alk immunohistochemistry and all but one by ALK FISH. In our experience, targeted next-generation sequencing is a reliable and timesaving tool for multiplexed detection of targetable rearrangements. Therefore, targeted next-generation sequencing represents an efficient alternative to time-consuming single target assays currently used in molecular pathology.

Published
2018

15. Cytology smears as excellent starting material for next-generation sequencing-based molecular testing of patients with adenocarcinoma of the lung

Author

Velizheva, Nadezda P, Rechsteiner, Markus P, Wong, Christine E, Zhong, Qing, Rössle, Matthias, Bode, Beata, Moch, Holger, Soltermann, Alex, Wild, Peter J, Tischler, Verena, University of Zurich, and Wild, Peter J

Subjects
Cancer Research, Oncology, 10049 Institute of Pathology and Molecular Pathology, 610 Medicine & health, 2730 Oncology, 1306 Cancer Research
Published
2017

16. Proteome Heterogeneity In Benign And Malignant Prostate Tissue

Author

Guo, Tiannan, Li, Li, Zhong, Qing, Rupp, Niels J., Charmpi, Konstantina, Wong, Christine E., Wagner, Ulrich, Rueschoff, Jan H., Jochum, Wolfram, Fankhauser, Christian, Saba, Karim, Poyet, Cedric, Wild, Peter, Aebersold, Ruedi, and Beyer, Andreas

Subjects
3. Good health
Abstract

Intra-tumor heterogeneity (ITH) has been characterized at the morphologic and genomic level. However, it is unclear how genomic heterogeneity is translated into functional proteome ITH. We addressed this question by performing a multi-region proteomic analysis of 60 biopsy-scale tissue samples from three prostate cancer patients using pressure cycling technology (PCT) and SWATH mass spectrometry. We quantified the degree of ITH for 1,906 proteins in malignant and benign tissue. The majority of proteins displayed a relatively low degree of ITH and benign tissue exhibited generally more complex patterns of ITH than malignant tissue. Further, we developed an ITH-corrected protein fold-change measure and demonstrated in an independent patient cohort that this new measure rescued potentially clinically relevant protein markers and stratified patients. This study established a strategy for quantifying proteome-scale ITH, generated a data resource of the proteomic ITH in prostate cancers, and demonstrated the value of considering ITH for tumor characterization. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 668858. This work was supported (in part) by the Swiss State Secretariat for Education, Research and Innovation (SERI) under contract number 15.0324-2. The opinions expressed and arguments employed therein do not necessarily reflect the official views of the Swiss Government.

Published
2016
Full Text
View/download PDF

20. Proteome Heterogeneity In Benign And Malignant Prostate Tissue

Author

Guo, Tiannan, Li, Li, Zhong, Qing, Rupp, Niels J., Charmpi, Konstantina, Wong, Christine E., Wagner, Ulrich, Rueschoff, Jan H., Jochum, Wolfram, Fankhauser, Christian, Saba, Karim, Poyet, Cedric, Wild, Peter, Aebersold, Ruedi, and Beyer, Andreas

Subjects
3. Good health
Abstract

Intra-tumor heterogeneity (ITH) has been characterized at the morphologic and genomic level. However, it is unclear how genomic heterogeneity is translated into functional proteome ITH. We addressed this question by performing a multi-region proteomic analysis of 60 biopsy-scale tissue samples from three prostate cancer patients using pressure cycling technology (PCT) and SWATH mass spectrometry. We quantified the degree of ITH for 1,906 proteins in malignant and benign tissue. The majority of proteins displayed a relatively low degree of ITH and benign tissue exhibited generally more complex patterns of ITH than malignant tissue. Further, we developed an ITH-corrected protein fold-change measure and demonstrated in an independent patient cohort that this new measure rescued potentially clinically relevant protein markers and stratified patients. This study established a strategy for quantifying proteome-scale ITH, generated a data resource of the proteomic ITH in prostate cancers, and demonstrated the value of considering ITH for tumor characterization. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 668858. This work was supported (in part) by the Swiss State Secretariat for Education, Research and Innovation (SERI) under contract number 15.0324-2. The opinions expressed and arguments employed therein do not necessarily reflect the official views of the Swiss Government., The information in this document is provided as is, and no guarantee or warranty is given that the information is fit for any particular purpose. The content of this document reflects only the author's view - the European Commission is not responsible for any use that may be made of the information it contains. The users use the information at their sole risk and liability.

Catalog

Books, media, physical & digital resources
See catalog results