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

G. Schleiermacher, J. Michon, A. Ribeiro, G. Pierron, V. Mosseri, H. Rubie, C. Munzer, J. Bénard, N. Auger, V. Combaret, I. Janoueix-Lerosey, A. Pearson, D. A. Tweddle, N. Bown, M. Gerrard, K. Wheeler, R. Noguera, E. Villamon, A. Cãete, V. CastelB. Marques, A. De Lacerda, G. P. Tonini, K. Mazzocco, R. Defferrari, B. De Bernardi, A. Di Cataldo, N. Van Roy, B. Brichard, R. Ladenstein, I. Ambros, P. Ambros, K. Beiske, O. Delattre, J. Couturier

Research output: Contribution to journalArticle

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 enroled 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) (P0.0001). 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, P0.0001, P0.04 and P0.0003, 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.

Original languageEnglish
Pages (from-to)1940-1948
Number of pages9
JournalBritish Journal of Cancer
Volume105
Issue number12
DOIs
Publication statusPublished - Dec 6 2011

Keywords

  • Genomic profile
  • Infants
  • Neuroblastoma
  • Prognosis
  • Segmental chromosome alterations

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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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., Cãete, A., ... Couturier, J. (2011). Segmental chromosomal alterations lead to a higher risk of relapse in infants with MYCN-non-amplified localised unresectable/disseminated neuroblastoma (a SIOPEN collaborative study). British Journal of Cancer, 105(12), 1940-1948. https://doi.org/10.1038/bjc.2011.472