Browsing by Author "Auger, N."
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- Segmental chromosomal alterations lead to a higher risk of relapse in infants with MYCN-non-amplified localised unresectable/disseminated neuroblastoma (a SIOPEN collaborative study).Publication . 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.; Castel, V.; Marques, B.; de Lacerda, A.; Tonini, G.P.; Mazzocco, K.; Defferrari, R.; de Bernardi, B.; di Cataldo, A.; van Roy, N.; Brichard, B.; Ladenstein, R.; Ambros, I.; Ambros, P.; Beiske, K.; Delattre, O.; Couturier, J.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.
