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Dormant SOX9-positi...
Dormant SOX9-positive cells behind MYC-driven medulloblastoma recurrence
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- Bolin, Sara, 1988- (author)
- Uppsala universitet,Neuroonkologi
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- Borgenvik, Anna (author)
- Uppsala universitet,Neuroonkologi
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- Savov, Vasil (author)
- Uppsala universitet,Neuroonkologi
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show more...
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- Holmberg Olausson, Karl (author)
- Uppsala universitet,Neuroonkologi
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- Zhao, Miao (author)
- Uppsala universitet,Neuroonkologi
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- Rosén, Gabriela (author)
- Uppsala universitet,Neuroonkologi
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- Hutter, Sonja (author)
- Uppsala universitet,Neuroonkologi
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- Garancher, Alexandra (author)
- umor Initiation & Maintenance Program, Sanford Burnham Prebys Medical Dis-covery Institute, La Jolla, USA.
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- Rahmanto, Aldwin Suryo (author)
- Departmentof Cell and Molecular Biology, Karolinska Institutet, Stockholm, Swe-den
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- Bergström, Tobias, 1980- (author)
- Uppsala universitet,Neuroonkologi
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- Mainwaring, Oliver (author)
- Uppsala universitet,Neuroonkologi
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- Sattanino, Damiana (author)
- Uppsala universitet,Neuroonkologi
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- Verbaan, Annemieke (author)
- Uppsala universitet,Neuroonkologi
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- Rusert, Jessica (author)
- Tumor Initiation & Maintenance Program, Sanford Burnham Prebys Medical Dis-covery Institute, La Jolla, USA
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- Sundström, Anders (author)
- Uppsala universitet,Neuroonkologi
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- Dang, Yonglong (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab
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- Wenz, Amelie (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab
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- Richardson, Stacey (author)
- Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK.
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- Fotaki, Grammatiki (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi
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- Giraud, Geraldine (author)
- Uppsala universitet,Neuroonkologi
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- Hill, Rebecca M (author)
- Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK.
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- Dubuc, Adrian M (author)
- The Arthur and Sonia Labatt Brain Tumor Research Centre, The Hospital for Sick Children, Toronto, Ontario, M5G 1X8, Canada.
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- Kalushkova, Antonia (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab
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- Remke, Marc (author)
- The Arthur and Sonia Labatt Brain Tumor Research Centre, The Hospital for Sick Children, Toronto, Ontario, M5G 1X8, Canada.
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- Čančer, Matko (author)
- Uppsala universitet,Neuroonkologi
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- Jernberg Wiklund, Helena (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab
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- Chen, Xingqi (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab
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- Taylor, Michael D (author)
- The Arthur and Sonia Labatt Brain Tumor Research Centre, The Hospital for Sick Children, Toronto, Ontario, M5G 1X8, Canada
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- Sangfelt, Olle (author)
- Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Swe-den.
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- Clifford, Steven C (author)
- Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK.
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- Schüller, Ulrich (author)
- Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Ham-burg, Germany. Department of Paediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. Research Institute Children’s Cancer Center Hamburg, Hamburg, Germany.
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- Wechsler-Reya, Robert J (author)
- Tumor Initiation & Maintenance Program, Sanford Burnham Prebys Medical Dis-covery Institute, La Jolla, USA.
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- Weishaupt, Holger (author)
- Uppsala universitet,Neuroonkologi
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- Swartling, Fredrik J., 1975- (author)
- Uppsala universitet,Neuroonkologi
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(creator_code:org_t)
- English.
- Related links:
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https://urn.kb.se/re...
Abstract
Subject headings
Close
- Tumor recurrence is a slow biological process involving therapy resistance, immune escape, and metastasis and is the leading cause of death in medulloblastoma, the most frequent malignant pediatric brain tumor. By studying paired primary-recurrent patient samples and patient-derived xenografts we identified a significant accumulation of SOX9-positive cells in relapses and metastases. They exist as rare, quiescent cells in Group 3 and Group 4 patients that constitute two-thirds of medulloblastoma. To follow relapse at the single-cell level we developed an inducible dual Tet model of MYC-driven MB, where MYC can be directed from treatment-sensitive bulk cells to resistant, dormant SOX9-positive cells by doxycycline. SOX9 promoted immune es-cape, DNA repair suppression and was essential for recurrence. Tumor cell dormancy was non-hierarchical, migratory, and depended on MYC suppression by SOX9 to promote relapse. By using computational modeling and treatment we further showed how doxorubicin and MGMT inhibitors are specifically targeting relapsing cells.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- SOX9
- medulloblastoma
- relapse
- recurrence
- MYCN
- mouse model
- pediatric cancer
- Oncology
- Onkologi
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Bolin, Sara, 198 ...
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Borgenvik, Anna
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Savov, Vasil
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Holmberg Olausso ...
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Zhao, Miao
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Rosén, Gabriela
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show more...
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Hutter, Sonja
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Garancher, Alexa ...
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Rahmanto, Aldwin ...
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Bergström, Tobia ...
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Mainwaring, Oliv ...
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Sattanino, Damia ...
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Verbaan, Annemie ...
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Rusert, Jessica
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Sundström, Ander ...
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Dang, Yonglong
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Wenz, Amelie
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Richardson, Stac ...
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Fotaki, Grammati ...
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Giraud, Geraldin ...
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Hill, Rebecca M
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Dubuc, Adrian M
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Kalushkova, Anto ...
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Remke, Marc
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Čančer, Matko
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Jernberg Wiklund ...
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Chen, Xingqi
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Taylor, Michael ...
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Sangfelt, Olle
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Clifford, Steven ...
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Schüller, Ulrich
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Wechsler-Reya, R ...
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Weishaupt, Holge ...
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Swartling, Fredr ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
- By the university
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Uppsala University