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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
Volume31
Issue23
Pages2927-35
Date Published2013 Aug 10
ISSN1527-7755
KeywordsAdolescent, Adult, Cerebellar Neoplasms, Child, Child, Preschool, Female, Gene Expression Profiling, Genes, p53, Humans, Infant, Male, Medulloblastoma, Middle Aged, Mutation, Prognosis, Young Adult
Abstract

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.

URLhttp://www.jco.org/cgi/pmidlookup?view=long&pmid=23835706
DOI10.1200/JCO.2012.48.5052
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/23835706?dopt=Abstract

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