Subgroup-Specific Prognostic Implications of TP53 Mutation in Medulloblastoma

N Zhukova, V Ramaswamy, M Remke, E Pfaff, DJH Shih, DC Martin, P Castelo-Branco, B Baskin, PN Ray, E Bouffet, AO von Bueren, DTW Jones, PA Northcott, D Sturm, TJ Pugh, SL Pomeroy, YJ Cho, T Pietsch, M Gessi, S RutkowskiL Bognar, A Klekner, BK Cho, SK Kim, KC Wang, CG Eberhart, M Fevre-Montange, M Fouladi, Pim French, J.M. Kros, WA Grajkowska, N Gupta, WA Weiss, P Hauser, N Jabado, A Jouvet, S Jung, T Kumabe, B Lach, JR Leonard, JB Rubin, LM Liau, L Massimi, IF Pollack, YS Ra, EG van Meir, K Zitterbart, U Schueller, RM Hill, JC Lindsey, EC Schwalbe, S Bailey, DW Ellison, C Hawkins, D Malkin, SC Clifford, A Korshunov, S Pfister, MD Taylor, U Tabori, Mirjam Kool

Research output: Contribution to journalArticleAcademicpeer-review

316 Citations (Scopus)

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 < .001). Patients with SHH/TP53 mutant tumors are almost exclusively between ages 5 and 18 years, dramatically different from the general SHH distribution (P < .001). Children with SHH/TP53 mutant tumors harbor 56% germline TP53 mutations, which are not observed in children with WNT/TP53 mutant tumors. Five-year overall survival (OS; +/- SE) wa 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. (C) 2013 by American Society of Clinical Oncology
Original languageEnglish
Pages (from-to)2927-+
JournalJournal of Clinical Oncology
Volume31
Issue number23
DOIs
Publication statusPublished - 2013

Fingerprint

Dive into the research topics of 'Subgroup-Specific Prognostic Implications of TP53 Mutation in Medulloblastoma'. Together they form a unique fingerprint.

Cite this