Tumoral TP53 and/or CDKN2A alterations are not reliable prognostic biomarkers in patients with localized Ewing sarcoma: A report from the Children's Oncology Group

for the Children's Oncology Group Ewing Sarcoma Biology Committee

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Background: A growing collection of retrospective studies have suggested that TP53 mutations and/or CDKN2A deletions have prognostic significance in Ewing sarcoma. We sought to evaluate these variables in patients with localized disease treated prospectively on a single Children's Oncology Group protocol. Procedure: Of the 568 patients enrolled on Children's Oncology Group protocol AEWS0031 (NCT00006734), 112 had tumor specimens of sufficient quality and quantity to allow for analysis of TP53 mutations status by DNA sequencing, and CDKN2A deletion by dual color fluorescent in situ hybridization. Results: Eight of 93 cases (8.6%) were found to have TP53 point mutations and 12 of 107 cases (11.2%) demonstrated homozygous CDKN2A deletion. Two cases were found to have an alteration in both genes. There was no significant difference in event-free survival of patients with TP53 mutations and/or CDKN2A deletions compared to patients with normal TP53/CDKN2A gene status, as demonstrated by log rank test (p = 0.58). Conclusions: Although previous retrospective studies suggest their significance, TP53 mutation and/or CDKN2A deletion are not reliable prognostic biomarkers in localized Ewing sarcoma. Pediatr Blood Cancer 2015;62:759-765.

Original languageEnglish (US)
Pages (from-to)759-765
Number of pages7
JournalPediatric Blood and Cancer
Volume62
Issue number5
DOIs
StatePublished - May 1 2015

Fingerprint

Ewing's Sarcoma
Biomarkers
Mutation
Retrospective Studies
p16 Genes
p53 Genes
Fluorescence In Situ Hybridization
DNA Sequence Analysis
Point Mutation
Disease-Free Survival
Neoplasms
Color
Genes

Keywords

  • Biomarker
  • Ewing sarcoma
  • Outcomes
  • Prognosis

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Oncology

Cite this

Tumoral TP53 and/or CDKN2A alterations are not reliable prognostic biomarkers in patients with localized Ewing sarcoma : A report from the Children's Oncology Group. / for the Children's Oncology Group Ewing Sarcoma Biology Committee.

In: Pediatric Blood and Cancer, Vol. 62, No. 5, 01.05.2015, p. 759-765.

Research output: Contribution to journalArticle

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abstract = "Background: A growing collection of retrospective studies have suggested that TP53 mutations and/or CDKN2A deletions have prognostic significance in Ewing sarcoma. We sought to evaluate these variables in patients with localized disease treated prospectively on a single Children's Oncology Group protocol. Procedure: Of the 568 patients enrolled on Children's Oncology Group protocol AEWS0031 (NCT00006734), 112 had tumor specimens of sufficient quality and quantity to allow for analysis of TP53 mutations status by DNA sequencing, and CDKN2A deletion by dual color fluorescent in situ hybridization. Results: Eight of 93 cases (8.6{\%}) were found to have TP53 point mutations and 12 of 107 cases (11.2{\%}) demonstrated homozygous CDKN2A deletion. Two cases were found to have an alteration in both genes. There was no significant difference in event-free survival of patients with TP53 mutations and/or CDKN2A deletions compared to patients with normal TP53/CDKN2A gene status, as demonstrated by log rank test (p = 0.58). Conclusions: Although previous retrospective studies suggest their significance, TP53 mutation and/or CDKN2A deletion are not reliable prognostic biomarkers in localized Ewing sarcoma. Pediatr Blood Cancer 2015;62:759-765.",
keywords = "Biomarker, Ewing sarcoma, Outcomes, Prognosis",
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T1 - Tumoral TP53 and/or CDKN2A alterations are not reliable prognostic biomarkers in patients with localized Ewing sarcoma

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AU - Lerman, Daniel M.

AU - Monument, Michael J.

AU - Mcilvaine, Elizabeth

AU - Liu, Xiao Qiong

AU - Huang, Dali

AU - Monovich, Laura

AU - Beeler, Natalie

AU - Gorlick, Richard G.

AU - Marina, Neyssa M.

AU - Womer, Richard B.

AU - Bridge, Julia A.

AU - Krailo, Mark D.

AU - Randall, R. Lor

AU - Lessnick, Stephen L.

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N2 - Background: A growing collection of retrospective studies have suggested that TP53 mutations and/or CDKN2A deletions have prognostic significance in Ewing sarcoma. We sought to evaluate these variables in patients with localized disease treated prospectively on a single Children's Oncology Group protocol. Procedure: Of the 568 patients enrolled on Children's Oncology Group protocol AEWS0031 (NCT00006734), 112 had tumor specimens of sufficient quality and quantity to allow for analysis of TP53 mutations status by DNA sequencing, and CDKN2A deletion by dual color fluorescent in situ hybridization. Results: Eight of 93 cases (8.6%) were found to have TP53 point mutations and 12 of 107 cases (11.2%) demonstrated homozygous CDKN2A deletion. Two cases were found to have an alteration in both genes. There was no significant difference in event-free survival of patients with TP53 mutations and/or CDKN2A deletions compared to patients with normal TP53/CDKN2A gene status, as demonstrated by log rank test (p = 0.58). Conclusions: Although previous retrospective studies suggest their significance, TP53 mutation and/or CDKN2A deletion are not reliable prognostic biomarkers in localized Ewing sarcoma. Pediatr Blood Cancer 2015;62:759-765.

AB - Background: A growing collection of retrospective studies have suggested that TP53 mutations and/or CDKN2A deletions have prognostic significance in Ewing sarcoma. We sought to evaluate these variables in patients with localized disease treated prospectively on a single Children's Oncology Group protocol. Procedure: Of the 568 patients enrolled on Children's Oncology Group protocol AEWS0031 (NCT00006734), 112 had tumor specimens of sufficient quality and quantity to allow for analysis of TP53 mutations status by DNA sequencing, and CDKN2A deletion by dual color fluorescent in situ hybridization. Results: Eight of 93 cases (8.6%) were found to have TP53 point mutations and 12 of 107 cases (11.2%) demonstrated homozygous CDKN2A deletion. Two cases were found to have an alteration in both genes. There was no significant difference in event-free survival of patients with TP53 mutations and/or CDKN2A deletions compared to patients with normal TP53/CDKN2A gene status, as demonstrated by log rank test (p = 0.58). Conclusions: Although previous retrospective studies suggest their significance, TP53 mutation and/or CDKN2A deletion are not reliable prognostic biomarkers in localized Ewing sarcoma. Pediatr Blood Cancer 2015;62:759-765.

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