WNT activation by lithium abrogates TP53 mutation associated radiation resistance in medulloblastoma

Nataliya Zhukova, Vijay Ramaswamy, Marc Remke, Dianna C. Martin, Pedro Castelo-Branco, Cindy H. Zhang, Michael Fraser, Ken Tse, Raymond Poon, David J H Shih, Berivan Baskin, Peter N. Ray, Eric Bouffet, Peter Dirks, Andre O. von Bueren, Elke Pfaff, Andrey Korshunov, David T W Jones, Paul A. Northcott, Marcel KoolTrevor J. Pugh, Scott L. Pomeroy, Yoon Jae Cho, Torsten Pietsch, Marco Gessi, Stefan Rutkowski, L. Bognár, Byung Kyu Cho, Charles G. Eberhart, Cecile F aure Conter, Maryam Fouladi, Pim J. French, Wieslawa A. Grajkowska, Nalin Gupta, P. Hauser, Nada Jabado, Alexandre Vasiljevic, Shin Jung, Seung Ki Kim, A. Klekner, Toshihiro Kumabe, Boleslaw Lach, Jeffrey R. Leonard, Linda M. Liau, Luca Massimi, Ian F. Pollack, Young S hin Ra, Joshua B. Rubin, Erwin G. Van Meir, Kyu Chang Wang, William A. Weiss, Karel Zitterbart, Robert G. Bristow, Benjamin Alman, Cynthia E. Hawkins, David Malkin, Steven C. Clifford, Stefan M. Pfister, Michael D. Taylor, Uri Tabori

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

TP53 mutations confer subgroup specific poor survival for children with medulloblastoma. We hypothesized that WNT activation which is associated with improved survival for such children abrogates TP53 related radioresistance and can be used to sensitize TP53 mutant tumors for radiation. We examined the subgroup-specific role of TP53 mutations in a cohort of 314 patients treated with radiation. TP53 wild-type or mutant human medulloblastoma cell-lines and normal neural stem cells were used to test radioresistance of TP53 mutations and the radiosensitizing effect of WNT activation on tumors and the developing brain. Children with WNT/TP53 mutant medulloblastoma had higher 5-year survival than those with SHH/TP53 mutant tumours (100% and 36.6%±8.7%, respectively (p

Original languageEnglish
Pages (from-to)174
Number of pages1
JournalActa neuropathologica communications
Volume2
DOIs
Publication statusPublished - 2014

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Medulloblastoma
Lithium
Radiation
Mutation
Survival
Radiation-Sensitizing Agents
Neural Stem Cells
Brain Neoplasms
Neoplasms
Cell Line

ASJC Scopus subject areas

  • Medicine(all)

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Zhukova, N., Ramaswamy, V., Remke, M., Martin, D. C., Castelo-Branco, P., Zhang, C. H., ... Tabori, U. (2014). WNT activation by lithium abrogates TP53 mutation associated radiation resistance in medulloblastoma. Acta neuropathologica communications, 2, 174. https://doi.org/10.1186/s40478-014-0174-y

WNT activation by lithium abrogates TP53 mutation associated radiation resistance in medulloblastoma. / Zhukova, Nataliya; Ramaswamy, Vijay; Remke, Marc; Martin, Dianna C.; Castelo-Branco, Pedro; Zhang, Cindy H.; Fraser, Michael; Tse, Ken; Poon, Raymond; Shih, David J H; Baskin, Berivan; Ray, Peter N.; Bouffet, Eric; Dirks, Peter; von Bueren, Andre O.; Pfaff, Elke; Korshunov, Andrey; Jones, David T W; Northcott, Paul A.; Kool, Marcel; Pugh, Trevor J.; Pomeroy, Scott L.; Cho, Yoon Jae; Pietsch, Torsten; Gessi, Marco; Rutkowski, Stefan; Bognár, L.; Cho, Byung Kyu; Eberhart, Charles G.; Conter, Cecile F aure; Fouladi, Maryam; French, Pim J.; Grajkowska, Wieslawa A.; Gupta, Nalin; Hauser, P.; Jabado, Nada; Vasiljevic, Alexandre; Jung, Shin; Kim, Seung Ki; Klekner, A.; Kumabe, Toshihiro; Lach, Boleslaw; Leonard, Jeffrey R.; Liau, Linda M.; Massimi, Luca; Pollack, Ian F.; Ra, Young S hin; Rubin, Joshua B.; Van Meir, Erwin G.; Wang, Kyu Chang; Weiss, William A.; Zitterbart, Karel; Bristow, Robert G.; Alman, Benjamin; Hawkins, Cynthia E.; Malkin, David; Clifford, Steven C.; Pfister, Stefan M.; Taylor, Michael D.; Tabori, Uri.

In: Acta neuropathologica communications, Vol. 2, 2014, p. 174.

Research output: Contribution to journalArticle

Zhukova, N, Ramaswamy, V, Remke, M, Martin, DC, Castelo-Branco, P, Zhang, CH, Fraser, M, Tse, K, Poon, R, Shih, DJH, Baskin, B, Ray, PN, Bouffet, E, Dirks, P, von Bueren, AO, Pfaff, E, Korshunov, A, Jones, DTW, Northcott, PA, Kool, M, Pugh, TJ, Pomeroy, SL, Cho, YJ, Pietsch, T, Gessi, M, Rutkowski, S, Bognár, L, Cho, BK, Eberhart, CG, Conter, CFA, Fouladi, M, French, PJ, Grajkowska, WA, Gupta, N, Hauser, P, Jabado, N, Vasiljevic, A, Jung, S, Kim, SK, Klekner, A, Kumabe, T, Lach, B, Leonard, JR, Liau, LM, Massimi, L, Pollack, IF, Ra, YSH, Rubin, JB, Van Meir, EG, Wang, KC, Weiss, WA, Zitterbart, K, Bristow, RG, Alman, B, Hawkins, CE, Malkin, D, Clifford, SC, Pfister, SM, Taylor, MD & Tabori, U 2014, 'WNT activation by lithium abrogates TP53 mutation associated radiation resistance in medulloblastoma', Acta neuropathologica communications, vol. 2, pp. 174. https://doi.org/10.1186/s40478-014-0174-y
Zhukova, Nataliya ; Ramaswamy, Vijay ; Remke, Marc ; Martin, Dianna C. ; Castelo-Branco, Pedro ; Zhang, Cindy H. ; Fraser, Michael ; Tse, Ken ; Poon, Raymond ; Shih, David J H ; Baskin, Berivan ; Ray, Peter N. ; Bouffet, Eric ; Dirks, Peter ; von Bueren, Andre O. ; Pfaff, Elke ; Korshunov, Andrey ; Jones, David T W ; Northcott, Paul A. ; Kool, Marcel ; Pugh, Trevor J. ; Pomeroy, Scott L. ; Cho, Yoon Jae ; Pietsch, Torsten ; Gessi, Marco ; Rutkowski, Stefan ; Bognár, L. ; Cho, Byung Kyu ; Eberhart, Charles G. ; Conter, Cecile F aure ; Fouladi, Maryam ; French, Pim J. ; Grajkowska, Wieslawa A. ; Gupta, Nalin ; Hauser, P. ; Jabado, Nada ; Vasiljevic, Alexandre ; Jung, Shin ; Kim, Seung Ki ; Klekner, A. ; Kumabe, Toshihiro ; Lach, Boleslaw ; Leonard, Jeffrey R. ; Liau, Linda M. ; Massimi, Luca ; Pollack, Ian F. ; Ra, Young S hin ; Rubin, Joshua B. ; Van Meir, Erwin G. ; Wang, Kyu Chang ; Weiss, William A. ; Zitterbart, Karel ; Bristow, Robert G. ; Alman, Benjamin ; Hawkins, Cynthia E. ; Malkin, David ; Clifford, Steven C. ; Pfister, Stefan M. ; Taylor, Michael D. ; Tabori, Uri. / WNT activation by lithium abrogates TP53 mutation associated radiation resistance in medulloblastoma. In: Acta neuropathologica communications. 2014 ; Vol. 2. pp. 174.
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abstract = "TP53 mutations confer subgroup specific poor survival for children with medulloblastoma. We hypothesized that WNT activation which is associated with improved survival for such children abrogates TP53 related radioresistance and can be used to sensitize TP53 mutant tumors for radiation. We examined the subgroup-specific role of TP53 mutations in a cohort of 314 patients treated with radiation. TP53 wild-type or mutant human medulloblastoma cell-lines and normal neural stem cells were used to test radioresistance of TP53 mutations and the radiosensitizing effect of WNT activation on tumors and the developing brain. Children with WNT/TP53 mutant medulloblastoma had higher 5-year survival than those with SHH/TP53 mutant tumours (100{\%} and 36.6{\%}±8.7{\%}, respectively (p",
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AU - Zhukova, Nataliya

AU - Ramaswamy, Vijay

AU - Remke, Marc

AU - Martin, Dianna C.

AU - Castelo-Branco, Pedro

AU - Zhang, Cindy H.

AU - Fraser, Michael

AU - Tse, Ken

AU - Poon, Raymond

AU - Shih, David J H

AU - Baskin, Berivan

AU - Ray, Peter N.

AU - Bouffet, Eric

AU - Dirks, Peter

AU - von Bueren, Andre O.

AU - Pfaff, Elke

AU - Korshunov, Andrey

AU - Jones, David T W

AU - Northcott, Paul A.

AU - Kool, Marcel

AU - Pugh, Trevor J.

AU - Pomeroy, Scott L.

AU - Cho, Yoon Jae

AU - Pietsch, Torsten

AU - Gessi, Marco

AU - Rutkowski, Stefan

AU - Bognár, L.

AU - Cho, Byung Kyu

AU - Eberhart, Charles G.

AU - Conter, Cecile F aure

AU - Fouladi, Maryam

AU - French, Pim J.

AU - Grajkowska, Wieslawa A.

AU - Gupta, Nalin

AU - Hauser, P.

AU - Jabado, Nada

AU - Vasiljevic, Alexandre

AU - Jung, Shin

AU - Kim, Seung Ki

AU - Klekner, A.

AU - Kumabe, Toshihiro

AU - Lach, Boleslaw

AU - Leonard, Jeffrey R.

AU - Liau, Linda M.

AU - Massimi, Luca

AU - Pollack, Ian F.

AU - Ra, Young S hin

AU - Rubin, Joshua B.

AU - Van Meir, Erwin G.

AU - Wang, Kyu Chang

AU - Weiss, William A.

AU - Zitterbart, Karel

AU - Bristow, Robert G.

AU - Alman, Benjamin

AU - Hawkins, Cynthia E.

AU - Malkin, David

AU - Clifford, Steven C.

AU - Pfister, Stefan M.

AU - Taylor, Michael D.

AU - Tabori, Uri

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