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| Status |
Public on Mar 13, 2018 |
| Title |
Copy number profiling of 556 high-risk neuroblastoma patients using aCGH or SNP arrays |
| Sample organism |
Homo sapiens |
| Experiment type |
Genome variation profiling by genome tiling array
Genome variation profiling by SNP array
Third-party reanalysis
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| Summary |
Purpose: 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. (i) Distal 6q losses were detected in 5.9% of patients and were associated with a ten-year survival probability of only 3.4%. (ii) Amplifications of regions not encompassing the MYCN locus were detected in 18% of patients and were associated with a ten-year survival probability of only 5.8%.
Conclusion: Using a unique large copy number dataset 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.
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| Overall design |
In an international collaborative effort joining nine neuroblastoma research groups, we collected DNA copy number data from 556 high risk neuroblastoma patients, enrolled in the SIOPEN, GPOH, COG and Japanese treatment protocols. High-risk was defined as either stage 4 and older than 1 year, or MYCN amplification (any age or stage). SIOPEN and GPOH data were combined to form the training cohort while COG and Japanese data were used as separate validation cohorts. These data include 92 samples previously reported on GEO, among which 68 samples from series GSE12494 and 24 samples from series GSE25771.
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| Contributor(s) |
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 |
| Citation(s) |
29514301 |
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| Submission date |
Aug 25, 2017 |
| Last update date |
Mar 14, 2018 |
| Contact name |
Katleen De Preter |
| E-mail(s) |
katleen.depreter@ugent.be
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| Organization name |
Ghent University
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| Department |
Center for Medical Genetics
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| Street address |
Corneel Heymanslaan 10
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| City |
Gent |
| ZIP/Postal code |
9000 |
| Country |
Belgium |
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| Supplementary file |
Size |
Download |
File type/resource |
| GSE103123_CytoScanHD_Array_CEL.tar.gz |
491.5 Mb |
(ftp)(http) |
TAR |
| GSE103123_README.txt |
1.9 Kb |
(ftp)(http) |
TXT |
| GSE103123_Sample_Details.xlsx |
68.7 Kb |
(ftp)(http) |
XLSX |
| GSE103123_custom_arrays_GH44_GH60.tar.gz |
6.1 Mb |
(ftp)(http) |
TAR |
| GSE103123_feature_extraction_files.tar.gz |
1.8 Gb |
(ftp)(http) |
TAR |
| GSE103123_processed_matrix_tables.tar.gz |
887.1 Mb |
(ftp)(http) |
TAR |
| Processed data are available on Series record |
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