@article{375e4375fcc247149b2c5556a7afaca3,
title = "Genomic amplifications and distal 6q loss: Novel markers for poor survival in high-risk neuroblastoma patients",
abstract = "Background: Neuroblastoma is characterized by substantial clinical heterogeneity. Despite intensive treatment, the survival rates of high-risk neuroblastoma patients are still disappointingly low. Somatic chromosomal copy number aberrations have been shown to be associated with patient outcome, particularly in low- and intermediate-risk neuroblastoma patients. To improve outcome prediction in high-risk neuroblastoma, we aimed to design a prognostic classificationmethod based on copy number aberrations. Methods: In an international collaboration, normalized high-resolution DNA copy number data (arrayCGH and SNP arrays) from 556 high-risk neuroblastomas obtained at diagnosis were collected from nine collaborative groups and segmented using the same method. We applied logistic and Cox proportional hazard regression to identify genomic aberrations associated with poor outcome. Results: In this study, we identified two types of copy number aberrations that are associated with extremely poor outcome. Distal 6q losses were detected in 5.9% of patients and were associated with a 10-year survival probability of only 3.4% (95% confidence interval [CI] = 0.5% to 23.3%, two-sided P = .002). Amplifications of regions not encompassing the MYCN locus were detected in 18.1% of patients and were associated with a 10-year survival probability of only 5.8% (95% CI = 1.5% to 22.2%, two-sided P < .001). Conclusions: Using a unique large copy number data set of high-risk neuroblastoma cases, we identified a small subset of high-risk neuroblastoma patients with extremely low survival probability that might be eligible for inclusion in clinical trials of new therapeutics. The amplicons may also nominate alternative treatments that target the amplified genes.",
author = "Pauline Depuydt and Valentina Boeva and Hocking, {Toby D.} and Robrecht Cannoodt and Ambros, {Inge M.} and Ambros, {Peter F.} and Shahab Asgharzadeh and Attiyeh, {Edward F.} and Val{\'e}rie Combaret and Raffaella Defferrari and Matthias Fischer and Barbara Hero and Hogarty, {Michael D.} and Irwin, {Meredith S.} and Jan Koster and Susan Kreissman and Ruth Ladenstein and Eve Lapouble and Genevi{\`e}ve Laureys and London, {Wendy B.} and Katia Mazzocco and Akira Nakagawara and Rosa Noguera and Miki Ohira and Park, {Julie R.} and Ulrike P{\"o}tschger and Jessica Theissen and Tonini, {Gian Paolo} and Dominique Valteau-Couanet and Luigi Varesio and Rogier Versteeg and Frank Speleman and Maris, {John M.} and Gudrun Schleiermacher and {De Preter}, Katleen",
note = "Funding Information: Nelia and Amadeo Barletta Foundation (FNAB), and the Association Hubert Gouin Enfance et Cancer. This study was also funded by the Associations Enfants et Sant{\'e}, Les Bagouz {\`a} Manon, Les amis de Claire. Funding was also obtained from SiRIC/INCa (grant number INCa-DGOS-4654), from the CEST of Institute Curie, and PHRC (grant number IC2007-09). Funding Information: EFA reports a grant from National Cancer Institute/National Institutes of Health and employment at Janssen R&D. MF reports honoraria at Novartis. BH reports grants from German Cancer Aid. JRP reports honoraria from Bristol Myer Squibb. The other authors have no disclosures. Funding Information: This work was supported by the National Cancer Institute Pediatric and Adolescent Solid Tumor Steering Committee for administrative support. PD was supported by the Fund for Scientific Research Flanders (Research project GOD8815N in the context of ERA-NET Transcan-2 cofound JTC 2014). VB was supported by the ATIP-Avenir Program, the ARC Foundation (grant number ARC-RAC16002KSAR15093KS), Worldwide Cancer Research Foundation (grant number WCR16-1294 R16100KK), and the “Who Am I?” laboratory of excellence ANR-11-LABX-0071, funded by the French Government through its “Investissement d{\textquoteright}Avenir” program operated by the French National Research Agency (ANR; grant number ANR-11-IDEX-0005-02). RC was supported by the Fund for Scientific Research Flanders. MF was supported by the Federal German Ministry of Education and Research (BMBF; grant numbers 01ZX1303A, 01ZX1603A, 01ZX1307D, and 01ZX1607D) and the German Cancer Aid (grant number 110122). RN was supported by the National Health Institute Carlos III and European Regional Development Fund (ISCIII&FEDER), Spain (grant numbers PI14/01008, RD12/0036/0020, and CB16/12/00484). JT was supported by the Deutsche Kinderkrebsstiftung (grant number DKS 2006.10). RV was supported by an ERC Advanced grant. GS received support from the Annenberg Foundation, the Publisher Copyright: {\textcopyright} The Author(s) 2018.",
year = "2018",
month = oct,
day = "1",
doi = "10.1093/jnci/djy022",
language = "English (US)",
volume = "110",
journal = "Journal of the National Cancer Institute",
issn = "0027-8874",
publisher = "Oxford University Press",
number = "10",
}