CASP8 SNP D302H (rs1045485) is associated with worse survival in MYCN-amplified neuroblastoma patients

PLoS One. 2014 Dec 11;9(12):e114696. doi: 10.1371/journal.pone.0114696. eCollection 2014.

Abstract

Background: Neuroblastoma is a pediatric cancer that exhibits a wide clinical spectrum ranging from spontaneous regression in low-risk patients to fatal disease in high-risk patients. The identification of single nucleotide polymorphisms (SNPs) may help explain the heterogeneity of neuroblastoma and assist in identifying patients at higher risk for poor survival. SNPs in the TP53 pathway are of special importance, as several studies have reported associations between TP53 pathway SNPs and cancer. Of note, less than 2% of neuroblastoma tumors have a TP53 mutation at diagnosis.

Patients and methods: We selected 21 of the most frequently studied SNPs in the TP53 pathway and evaluated their association with outcome in 500 neuroblastoma patients using TaqMan allelic discrimination assays.

Results and conclusion: We investigated the impact of 21 SNPs on overall survival, event-free survival, age at diagnosis, MYCN status, and stage of the disease in 500 neuroblastoma patients. A missense SNP in exon 10 of the CASP8 gene SNP D302H was associated with worse overall and event-free survival in patients with MYCN-amplified neuroblastoma tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Caspase 8 / genetics*
  • Disease-Free Survival
  • Gene Amplification*
  • Gene Expression Regulation, Neoplastic
  • Genotyping Techniques
  • Humans
  • Infant
  • N-Myc Proto-Oncogene Protein
  • Neoplasm Staging
  • Neuroblastoma / diagnosis*
  • Neuroblastoma / genetics*
  • Neuroblastoma / pathology
  • Nuclear Proteins / genetics*
  • Oncogene Proteins / genetics*
  • Polymorphism, Single Nucleotide*

Substances

  • MYCN protein, human
  • N-Myc Proto-Oncogene Protein
  • Nuclear Proteins
  • Oncogene Proteins
  • CASP8 protein, human
  • Caspase 8

Grants and funding

AR is supported by a PhD fellowship from the Ghent University research fund (BOF; 01D02210). TVM is a postdoctoral fellow of the FWO (12B9912N). RN is supported by FIS (contract PI10/15) and RTICC (contracts RD06/0020/0102; RD12/0036/0020), Instituto Carlos III Madrid & ERDF, Spain. Italian Neuroblastoma Foundation supported the Italian samples collection and preparation. This work was supported by the BOF, the FWO, the Childhood Cancer Fund, and the National Cancer Plan of the Belgian State (Action 29). The study sponsors have no role in the study design, in the collection, analysis and interpretation of data; in the writing of the manuscript; or in the decision to submit the manuscript for publication.