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Genomic amplifications and distal 6q loss : novel markers for poor survival in high-risk neuroblastoma patients

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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 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.
Keywords
COPY NUMBER, OUTCOME PREDICTION, CLASSIFICATION, AGE, DNA, STRATIFICATION, ABNORMALITIES, ACCUMULATION, DELINEATION, INTEGRATION

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Chicago
Depuydt, Pauline, Valentina Boeva, Toby D Hocking, Robrecht Cannoodt, Inge M Ambros, Peter F Ambros, Shahab Asgharzadeh, et al. 2018. “Genomic Amplifications and Distal 6q Loss : Novel Markers for Poor Survival in High-risk Neuroblastoma Patients.” Jnci-journal of the National Cancer Institute 110 (10).
APA
Depuydt, Pauline, Boeva, V., Hocking, T. D., Cannoodt, R., Ambros, I. M., Ambros, P. F., Asgharzadeh, S., et al. (2018). Genomic amplifications and distal 6q loss : novel markers for poor survival in high-risk neuroblastoma patients. JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 110(10).
Vancouver
1.
Depuydt P, Boeva V, Hocking TD, Cannoodt R, Ambros IM, Ambros PF, et al. Genomic amplifications and distal 6q loss : novel markers for poor survival in high-risk neuroblastoma patients. JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE. 2018;110(10).
MLA
Depuydt, Pauline, Valentina Boeva, Toby D Hocking, et al. “Genomic Amplifications and Distal 6q Loss : Novel Markers for Poor Survival in High-risk Neuroblastoma Patients.” JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE 110.10 (2018): n. pag. Print.
@article{8554860,
  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 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.},
  articleno    = {djy022},
  author       = {Depuydt, Pauline and Boeva, Valentina and Hocking, Toby D and Cannoodt, Robrecht and Ambros, Inge M and Ambros, Peter F and Asgharzadeh, Shahab and Attiyeh, Edward F and Combaret, Valérie and Defferrari, Raffaella and Fischer, Matthias and Hero, Barbara and Hogarty, Michael D and Irwin, Meredith S and Koster, Jan and Kreissman, Susan and Ladenstein, Ruth and Lapouble, Eve and Laureys, Genevieve and London, Wendy B and Mazzocco, Katia and Nakagawara, Akira and Noguera, Rosa and Ohira, Miki and Park, Julie R and Pötschger, Ulrike and Theissen, Jessica and Tonini, Gian Paolo and Valteau-Couanet, Dominique and Varesio, Luigi and Versteeg, Rogier and Speleman, Franki and Maris, John M and Schleiermacher, Gudrun and De Preter, Katleen},
  issn         = {0027-8874},
  journal      = {JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE},
  keywords     = {COPY NUMBER,OUTCOME PREDICTION,CLASSIFICATION,AGE,DNA,STRATIFICATION,ABNORMALITIES,ACCUMULATION,DELINEATION,INTEGRATION},
  language     = {eng},
  number       = {10},
  pages        = {10},
  title        = {Genomic amplifications and distal 6q loss : novel markers for poor survival in high-risk neuroblastoma patients},
  url          = {http://dx.doi.org/10.1093/jnci/djy022},
  volume       = {110},
  year         = {2018},
}

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