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

Ali Rihani; Bram De Wilde; Fjoralba Zeka; Geneviève Laureys; Nadine Francotte; Gian Paolo Tonini; Simona Coco; Rogier Versteeg; Rosa Noguera; Johannes H Schulte; Angelika Eggert; Raymond L Stallings; Frank Speleman; Jo Vandesompele; Tom Van Maerken

doi:10.1371/journal.pone.0114696

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.

Authors

Affiliations

¹ Center for Medical Genetics, Ghent University, Ghent, Belgium.
² Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, Ghent University Hospital, Ghent, Belgium.
³ Département de pédiatrie, hémato-oncologie, SUHOPL- CHC (Service Universitaire d'HématoOncologie Pédiatrique Centre Hospitalier Chrétien) Espérance, St Nicolas Belgium.
⁴ Neuroblastoma Laboratory, Onco/Hematology Laboratory, Department of Women's and Children's Health, University of Padua, Pediatric Research Institute, Fondazione Città della Speranza, Padua, Italy.
⁵ Lung Cancer Unit, IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico), Azienda Ospedaliera Universitaria San Martino - IST (Istituto Nazionale per la Ricerca sul Cancro), Genoa, Italy.
⁶ Departement of Human Genetics, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
⁷ Department of Pathology, Medical School, University of Valencia, Valencia, Spain.
⁸ German Cancer Consortium (DKTK), Germany; Translational Neuro-Oncology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Essen, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Pediatric Oncology and Haematology, University Children's Hospital Essen, Essen, Germany; Centre for Medical Biotechnology, University Duisburg-Essen, Essen, Germany.
⁹ Department of Pediatric Oncology and Haematology, University Children's Hospital Essen, Essen, Germany.
¹⁰ Department of Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, and National Children's Research Centre, Dublin, Ireland.

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.