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Statements

Subject Item
n2:RIV%2F65269705%3A_____%2F13%3A%230002225%21RIV14-MZ0-65269705
rdf:type
skos:Concept n15:Vysledek
rdfs:seeAlso
http://jco.ascopubs.org/content/31/23/2927.long
dcterms:description
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/7P53 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/7P53 mutant tumors. Five-year overall survival (OS;+/- SE) was 41 % +/- 9% and 81 % +/- 5% for patients with SHH medulloblastomas with and without TP53 mutations, respectively (P <.001). Furthermore, TP53 mutations accounted for 72% of deaths in children older than 5 years with SHH medulloblastomas. In contrast, 5-year OS rates were 90% +/- 9% and 97% +/- 3% for patients with WNT tumors with and without TP53 mutations (P = .21). Multivariate analysis revealed that TP53 status was the most important risk factor for SHH medulloblastoma. Survival rates in the validation cohort mimicked the discovery results, revealing that poor survival of TP53 mutations is restricted to patients with SHH medulloblastomas (P = .012) and not WNT tumors. 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. 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/7P53 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/7P53 mutant tumors. Five-year overall survival (OS;+/- SE) was 41 % +/- 9% and 81 % +/- 5% for patients with SHH medulloblastomas with and without TP53 mutations, respectively (P <.001). Furthermore, TP53 mutations accounted for 72% of deaths in children older than 5 years with SHH medulloblastomas. In contrast, 5-year OS rates were 90% +/- 9% and 97% +/- 3% for patients with WNT tumors with and without TP53 mutations (P = .21). Multivariate analysis revealed that TP53 status was the most important risk factor for SHH medulloblastoma. Survival rates in the validation cohort mimicked the discovery results, revealing that poor survival of TP53 mutations is restricted to patients with SHH medulloblastomas (P = .012) and not WNT tumors. 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.
dcterms:title
Subgroup-specific prognostic implications of TP53 mutation in medulloblastoma Subgroup-specific prognostic implications of TP53 mutation in medulloblastoma
skos:prefLabel
Subgroup-specific prognostic implications of TP53 mutation in medulloblastoma Subgroup-specific prognostic implications of TP53 mutation in medulloblastoma
skos:notation
RIV/65269705:_____/13:#0002225!RIV14-MZ0-65269705
n15:predkladatel
n16:ico%3A65269705
n3:aktivita
n13:I n13:V
n3:aktivity
I, V
n3:cisloPeriodika
23
n3:dodaniDat
n4:2014
n3:domaciTvurceVysledku
n11:5658179
n3:druhVysledku
n12:J
n3:duvernostUdaju
n14:S
n3:entitaPredkladatele
n18:predkladatel
n3:idSjednocenehoVysledku
108857
n3:idVysledku
RIV/65269705:_____/13:#0002225
n3:jazykVysledku
n8:eng
n3:klicovaSlova
Craniospinal radiotherapy; tumors; p53
n3:klicoveSlovo
n10:tumors n10:p53 n10:Craniospinal%20radiotherapy
n3:kodStatuVydavatele
US - Spojené státy americké
n3:kontrolniKodProRIV
[39ECE7E1B325]
n3:nazevZdroje
Journal of clinical oncology
n3:obor
n7:FD
n3:pocetDomacichTvurcuVysledku
1
n3:pocetTvurcuVysledku
61
n3:rokUplatneniVysledku
n4:2013
n3:svazekPeriodika
31
n3:tvurceVysledku
Zitterbart, Karel
n3:wos
000330539300018
s:issn
0732-183X
s:numberOfPages
9