1. Segmental chromosomal alterations lead to a higher risk of relapse in infants with MYCN-non-amplified localised unresectable/disseminated neuroblastoma (a SIOPEN collaborative study).
- Author
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Schleiermacher, G, Michon, J, Ribeiro, A, Pierron, G, Mosseri, V, Rubie, H, Munzer, C, Bénard, J, Auger, N, Combaret, V, Janoueix-Lerosey, I, Pearson, A, Tweddle, D A, Bown, N, Gerrard, M, Wheeler, K, Noguera, R, Villamon, E, Cañete, A, and Castel, V
- Subjects
NEUROBLASTOMA ,CHROMOSOMES ,TUMORS ,GENOMICS ,NERVOUS system tumors ,MULTIVARIATE analysis ,CHROMOSOME abnormalities ,COMPARATIVE studies ,LONGITUDINAL method ,RESEARCH methodology ,MEDICAL cooperation ,PROGNOSIS ,PROTEINS ,RESEARCH ,SURVIVAL analysis (Biometry) ,DISEASE relapse ,EVALUATION research ,NUCLEAR proteins - Abstract
Background: In neuroblastoma (NB), the presence of segmental chromosome alterations (SCAs) is associated with a higher risk of relapse.Methods: In order to analyse the role of SCAs in infants with localised unresectable/disseminated NB without MYCN amplification, we have performed an array CGH analysis of tumours from infants enrolled in the prospective European INES trials.Results: Tumour samples from 218 out of 300 enroled patients could be analysed. Segmental chromosome alterations were observed in 11%, 20% and 59% of infants enroled in trials INES99.1 (localised unresectable NB), INES99.2 (stage 4s) and INES99.3 (stage 4) (P<0.0001). Progression-free survival was poorer in patients whose tumours harboured SCA, in the whole population and in trials INES99.1 and INES99.2, in the absence of clinical symptoms (log-rank test, P=0.0001, P=0.04 and P=0.0003, respectively). In multivariate analysis, a SCA genomic profile was the strongest predictor of poorer progression-free survival.Conclusion: In infants with stage 4s MYCN-non-amplified NB, a SCA genomic profile identifies patients who will require upfront treatment even in the absence of other clinical indication for therapy, whereas in infants with localised unresectable NB, a genomic profile characterised by the absence of SCA identifies patients in whom treatment reduction might be possible. These findings will be implemented in a future international trial. [ABSTRACT FROM AUTHOR]- Published
- 2011
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