Depuydt, Pauline, Boeva, Valentina ORCID: 0000-0002-4382-7185, Hocking, Toby D., Cannoodt, Robrecht ORCID: 0000-0003-3641-729X, Ambros, Inge M., Ambros, Peter F. ORCID: 0000-0002-5507-7211, Asgharzadeh, Shahab, Attiyeh, Edward F., Combaret, Valerie, Defferrari, Raffaella, Fischer, Matthias, Hero, Barbara, Hogarty, Michael D., Irwin, Meredith S., Koster, Jan ORCID: 0000-0002-0890-7585, Kreissman, Susan, Ladenstein, Ruth, Lapouble, Eve, Laureys, Genevieve, London, Wendy B., Mazzocco, Katia ORCID: 0000-0002-6599-5681, Nakagawara, Akira, Noguera, Rosa, Ohira, Miki, Park, Julie R., Poetschger, Ulrike, Theissen, Jessica, Tonini, Gian Paolo, Valteau-Couanet, Dominique, Varesio, Luigi, Versteeg, Rogier ORCID: 0000-0001-7172-0388, Speleman, Frank, Maris, John M., Schleiermacher, Gudrun and De Preter, Katleen (2018). Genomic Amplifications and Distal 6q Loss: Novel Markers for Poor Survival in High-risk Neuroblastoma Patients. JNCI-J. Natl. Cancer Inst., 110 (10). CARY: OXFORD UNIV PRESS INC. ISSN 1460-2105

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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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Depuydt, PaulineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Boeva, ValentinaUNSPECIFIEDorcid.org/0000-0002-4382-7185UNSPECIFIED
Hocking, Toby D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cannoodt, RobrechtUNSPECIFIEDorcid.org/0000-0003-3641-729XUNSPECIFIED
Ambros, Inge M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ambros, Peter F.UNSPECIFIEDorcid.org/0000-0002-5507-7211UNSPECIFIED
Asgharzadeh, ShahabUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Attiyeh, Edward F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Combaret, ValerieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Defferrari, RaffaellaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fischer, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hero, BarbaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hogarty, Michael D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Irwin, Meredith S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koster, JanUNSPECIFIEDorcid.org/0000-0002-0890-7585UNSPECIFIED
Kreissman, SusanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ladenstein, RuthUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lapouble, EveUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Laureys, GenevieveUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
London, Wendy B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mazzocco, KatiaUNSPECIFIEDorcid.org/0000-0002-6599-5681UNSPECIFIED
Nakagawara, AkiraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Noguera, RosaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ohira, MikiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Park, Julie R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Poetschger, UlrikeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Theissen, JessicaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tonini, Gian PaoloUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Valteau-Couanet, DominiqueUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Varesio, LuigiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Versteeg, RogierUNSPECIFIEDorcid.org/0000-0001-7172-0388UNSPECIFIED
Speleman, FrankUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Maris, John M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schleiermacher, GudrunUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
De Preter, KatleenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-169965
DOI: 10.1093/jnci/djy022
Journal or Publication Title: JNCI-J. Natl. Cancer Inst.
Volume: 110
Number: 10
Date: 2018
Publisher: OXFORD UNIV PRESS INC
Place of Publication: CARY
ISSN: 1460-2105
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
COPY NUMBER; OUTCOME PREDICTION; CLASSIFICATION; AGE; DNA; STRATIFICATION; ABNORMALITIES; ACCUMULATION; DELINEATION; INTEGRATIONMultiple languages
OncologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/16996

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