Segmental chromosomal alterations lead to a higher risk of relapse in infants with MYCN-non-amplified localised unresectable/disseminated neuroblastoma (a SIOPEN collaborative study).

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.2012-03-152012-03-152011-12Br J Cancer. 2011 Dec 6;105(12):1940-8. Epub 2011 Nov 100007-0920doi: 10.1038/bjc.2011.472.http://hdl.handle.net/10400.18/794BACKGROUND: 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.engDoenças GenéticasNeuroblastomaSegmental Chromosome AlterationsHigh RiskSegmental chromosomal alterations lead to a higher risk of relapse in infants with MYCN-non-amplified localised unresectable/disseminated neuroblastoma (a SIOPEN collaborative study).journal article