Genomic Amplifications and Distal 6q Loss: Novel Markers for Poor Survival in High-risk Neuroblastoma Patients.

Published

Journal Article

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 classification method 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.

Full Text

Duke Authors

Cited Authors

  • Depuydt, P; Boeva, V; Hocking, TD; Cannoodt, R; Ambros, IM; Ambros, PF; Asgharzadeh, S; Attiyeh, EF; Combaret, V; Defferrari, R; Fischer, M; Hero, B; Hogarty, MD; Irwin, MS; Koster, J; Kreissman, S; Ladenstein, R; Lapouble, E; Laureys, G; London, WB; Mazzocco, K; Nakagawara, A; Noguera, R; Ohira, M; Park, JR; Pötschger, U; Theissen, J; Tonini, GP; Valteau-Couanet, D; Varesio, L; Versteeg, R; Speleman, F; Maris, JM; Schleiermacher, G; De Preter, K

Published Date

  • October 1, 2018

Published In

Volume / Issue

  • 110 / 10

Start / End Page

  • 1084 - 1093

PubMed ID

  • 29514301

Pubmed Central ID

  • 29514301

Electronic International Standard Serial Number (EISSN)

  • 1460-2105

Digital Object Identifier (DOI)

  • 10.1093/jnci/djy022

Language

  • eng

Conference Location

  • United States