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1 Department of Pediatrics, Division of Hematology and Oncology, Baylor College of Medicine, Houston, USA.
2 Brain Tumor Program, Cancer and Hematology Centers, Texas Children's Hospital, Houston, USA.
3 Department of Neurosurgery, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, EPE, Lisbon, Portugal.
4 Department of Developmental and Stem Cell Biology and Regenerative Medicine, The Hospital for Sick Children, Toronto, Canada.
5 Arthur and Sonia Labatt Brain Tumor Research Center, The Hospital for Sick Children, Toronto, Canada.
6 Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.
7 Department of Neurosurgery, The Hospital for Sick Children, Toronto, Canada.
8 Department of Neurological Surgery, Children's Hospital, University of Pittsburgh School of Medicine, Pittsburgh, USA.
9 Department of Pediatrics, Division of Hematology and Oncology, Baylor College of Medicine, Houston, USA. stephen.mack@bcm.edu.
10 Brain Tumor Program, Cancer and Hematology Centers, Texas Children's Hospital, Houston, USA. stephen.mack@bcm.edu.
11 Department of Developmental and Stem Cell Biology and Regenerative Medicine, The Hospital for Sick Children, Toronto, Canada. james.rutka@sickkids.ca.
12 Arthur and Sonia Labatt Brain Tumor Research Center, The Hospital for Sick Children, Toronto, Canada. james.rutka@sickkids.ca.
13 Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada. james.rutka@sickkids.ca.
14 Department of Neurosurgery, The Hospital for Sick Children, Toronto, Canada. james.rutka@sickkids.ca.
1 Department of Pediatrics, Division of Hematology and Oncology, Baylor College of Medicine, Houston, USA.
2 Brain Tumor Program, Cancer and Hematology Centers, Texas Children's Hospital, Houston, USA.
3 Department of Neurosurgery, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, EPE, Lisbon, Portugal.
4 Department of Developmental and Stem Cell Biology and Regenerative Medicine, The Hospital for Sick Children, Toronto, Canada.
5 Arthur and Sonia Labatt Brain Tumor Research Center, The Hospital for Sick Children, Toronto, Canada.
6 Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.
7 Department of Neurosurgery, The Hospital for Sick Children, Toronto, Canada.
8 Department of Neurological Surgery, Children's Hospital, University of Pittsburgh School of Medicine, Pittsburgh, USA.
9 Department of Pediatrics, Division of Hematology and Oncology, Baylor College of Medicine, Houston, USA. stephen.mack@bcm.edu.
10 Brain Tumor Program, Cancer and Hematology Centers, Texas Children's Hospital, Houston, USA. stephen.mack@bcm.edu.
11 Department of Developmental and Stem Cell Biology and Regenerative Medicine, The Hospital for Sick Children, Toronto, Canada. james.rutka@sickkids.ca.
12 Arthur and Sonia Labatt Brain Tumor Research Center, The Hospital for Sick Children, Toronto, Canada. james.rutka@sickkids.ca.
13 Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada. james.rutka@sickkids.ca.
14 Department of Neurosurgery, The Hospital for Sick Children, Toronto, Canada. james.rutka@sickkids.ca.
The authors declare that they have no competing interests.
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Figures
Fig. 1
A transposon-mutagenesis system to identify…
Fig. 1
A transposon-mutagenesis system to identify genes mediating Foretinib resistance in Medulloblastoma. a A…
Fig. 1
A transposon-mutagenesis system to identify genes mediating Foretinib resistance in Medulloblastoma. a A schematic describing the steps used to treat medulloblastoma-bearing mice with Foretinib and the identification of transposon insertion sites. b A Kaplan-Meier plot demonstrating significant improvement in overall survival in mice receiving Foretinib treatment
Fig. 2
Transposon insertion patterns are divergent…
Fig. 2
Transposon insertion patterns are divergent in primary medulloblastoma receiving Foretinib therapy. a A…
Fig. 2
Transposon insertion patterns are divergent in primary medulloblastoma receiving Foretinib therapy. a A Venn diagram illustrating the number of statistically significant gCISs exclusive or shared gCISs between vehicle (n = 14) and Foretinib (n = 12) treated primary medulloblastoma. b A table showing the Top 20 statistically significant Foretinib resistance genes in primary medulloblastoma. Highlighted in red are genes which have been reported to be mutated in cancer when compared against the COSMIC database. c Examples of transposon insertions in Cdh2 and Pten and their direction of orientation (red = anti-sense, blue = sense) relative to direction transcription (green). d Pathway analysis of Foretinib-resistance genes in primary medulloblastoma identified using GeneMania
Fig. 3
Divergent patterns of transposon insertions…
Fig. 3
Divergent patterns of transposon insertions in metastatic medulloblastoma following Foretinib therapy. a A…
Fig. 3
Divergent patterns of transposon insertions in metastatic medulloblastoma following Foretinib therapy. a A Venn diagram illustrating the number of statistically significant gCISs identified as exclusive or shared between primary (n = 14) and metastatic medulloblastoma (n = 26). b A Venn diagram illustrating the number of statistically significant gCISs exclusive or shared gCISs between vehicle (n = 26) and Foretinib treated metastatic medulloblastoma (n = 22). c A Venn diagram comparing the gCISs between primary (n = 12) and metastatic (n = 22) Foretinib treated medulloblastoma. d A table showing the Top 20 statistically significant Foretinib resistance genes in metastatic medulloblastoma. Highlighted in red are genes, which have been reported to be mutated in cancer when compared against the COSMIC database. e Examples of transposon insertions in Basp1 and Fcgr4 and their direction of orientation (red = anti-sense, blue = sense) relative to direction transcription (green). f Pathway analysis of Foretinib-resistance genes in metastatic medulloblastoma identified using GeneMania
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