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Combined MYC and P5...
Combined MYC and P53 Defects Emerge at Medulloblastoma Relapse and Define Rapidly Progressive, Therapeutically Targetable Disease
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Hill, Rebecca M. (author)
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Kuijper, Sanne (author)
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Lindsey, Janet C. (author)
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Petrie, Kevin (author)
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Schwalbe, Ed C. (author)
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Barker, Karen (author)
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Boult, Jessica K. R. (author)
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Williamson, Daniel (author)
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Ahmad, Zai (author)
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Hallsworth, Albert (author)
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Ryan, Sarra L. (author)
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Poon, Evon (author)
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Robinson, Simon P. (author)
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Ruddle, Ruth (author)
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Raynaud, Florence I. (author)
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Howell, Louise (author)
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Kwok, Colin (author)
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Joshi, Abhijit (author)
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Nicholson, Sarah Leigh (author)
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Crosier, Stephen (author)
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Ellison, David W. (author)
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Wharton, Stephen B. (author)
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Robson, Keith (author)
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Michalski, Antony (author)
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Hargrave, Darren (author)
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Jacques, Thomas S. (author)
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Pizer, Barry (author)
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Bailey, Simon (author)
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- Swartling, Fredrik J. (author)
- Uppsala universitet,Neuroonkologi
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Weiss, William A. (author)
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Chesler, Louis (author)
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Clifford, Steven C. (author)
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(creator_code:org_t)
- Elsevier BV, 2015
- 2015
- English.
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In: Cancer Cell. - : Elsevier BV. - 1535-6108 .- 1878-3686. ; 27:1, s. 72-84
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https://uu.diva-port... (primary) (Raw object)
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http://www.cell.com/...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- We undertook a comprehensive clinical and biological investigation of serial medulloblastoma biopsies obtained at diagnosis and relapse. Combined MYC family amplifications and P53 pathway defects commonly emerged at relapse, and all patients in this group died of rapidly progressive disease postrelapse. To study this interaction, we investigated a transgenic model of MYCN-driven medulloblastoma and found spontaneous development of Trp53 inactivating mutations. Abrogation of p53 function in this model produced aggressive tumors that mimicked characteristics of relapsed human tumors with combined P53-MYC dysfunction. Restoration of p53 activity and genetic and therapeutic suppression of MYCN all reduced tumor growth and prolonged survival. Our findings identify P53-MYC interactions at medulloblastoma relapse as biomarkers of clinically aggressive disease that may be targeted therapeutically.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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Hill, Rebecca M.
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Kuijper, Sanne
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Lindsey, Janet C ...
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Petrie, Kevin
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Schwalbe, Ed C.
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Barker, Karen
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show more...
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Boult, Jessica K ...
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Williamson, Dani ...
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Ahmad, Zai
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Hallsworth, Albe ...
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Ryan, Sarra L.
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Poon, Evon
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Robinson, Simon ...
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Ruddle, Ruth
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Raynaud, Florenc ...
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Howell, Louise
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Kwok, Colin
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Joshi, Abhijit
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Nicholson, Sarah ...
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Crosier, Stephen
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Ellison, David W ...
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Wharton, Stephen ...
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Robson, Keith
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Michalski, Anton ...
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Hargrave, Darren
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Jacques, Thomas ...
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Pizer, Barry
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Bailey, Simon
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Swartling, Fredr ...
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Weiss, William A ...
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Chesler, Louis
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Clifford, Steven ...
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show less...
- About the subject
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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 ...
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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 Neurology
- Articles in the publication
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Cancer Cell
- By the university
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Uppsala University