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J Clin Oncol DOI:10.1200/JCO.2012.48.5052

Subgroup-specific prognostic implications of TP53 mutation in medulloblastoma.

Publication TypeJournal Article
Year of Publication2013
AuthorsZhukova, N, Ramaswamy, V, Remke, M, Pfaff, E, Shih, DJH, Martin, DC, Castelo-Branco, P, Baskin, B, Ray, PN, Bouffet, E, von Bueren, AO, Jones, DTW, Northcott, PA, Kool, M, Sturm, D, Pugh, TJ, Pomeroy, SL, Cho, Y-J, Pietsch, T, Gessi, M, Rutkowski, S, Bognar, L, Klekner, A, Cho, B-K, Kim, S-K, Wang, K-C, Eberhart, CG, Fevre-Montange, M, Fouladi, M, French, PJ, Kros, M, Grajkowska, WA, Gupta, N, Weiss, WA, Hauser, P, Jabado, N, Jouvet, A, Jung, S, Kumabe, T, Lach, B, Leonard, JR, Rubin, JB, Liau, LM, Massimi, L, Pollack, IF, Ra, YShin, Van Meir, EG, Zitterbart, K, Schüller, U, Hill, RM, Lindsey, JC, Schwalbe, EC, Bailey, S, Ellison, DW, Hawkins, C, Malkin, D, Clifford, SC, Korshunov, A, Pfister, S, Taylor, MD, Tabori, U
JournalJ Clin Oncol
Date Published2013 Aug 10
KeywordsAdolescent, Adult, Cerebellar Neoplasms, Child, Child, Preschool, Female, Gene Expression Profiling, Genes, p53, Humans, Infant, Male, Medulloblastoma, Middle Aged, Mutation, Prognosis, Young Adult

PURPOSE: Reports detailing the prognostic impact of TP53 mutations in medulloblastoma offer conflicting conclusions. We resolve this issue through the inclusion of molecular subgroup profiles.

PATIENTS AND METHODS: We determined subgroup affiliation, TP53 mutation status, and clinical outcome in a discovery cohort of 397 medulloblastomas. We subsequently validated our results on an independent cohort of 156 medulloblastomas.

RESULTS: TP53 mutations are enriched in wingless (WNT; 16%) and sonic hedgehog (SHH; 21%) medulloblastomas and are virtually absent in subgroups 3 and 4 tumors (P

CONCLUSION: Subgroup-specific analysis reconciles prior conflicting publications and confirms that TP53 mutations are enriched among SHH medulloblastomas, in which they portend poor outcome and account for a large proportion of treatment failures in these patients.


Alternate JournalJ. Clin. Oncol.
PubMed ID23835706
PubMed Central IDPMC4878050
Grant ListP30 HD018655 / HD / NICHD NIH HHS / United States
R01 CA109467 / CA / NCI NIH HHS / United States
/ / Cancer Research UK / United Kingdom