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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)

Lookup NU author(s): Professor Deborah Tweddle, Dr Katia Mazzocco

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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) (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. British Journal of Cancer (2011) 105, 1940-1948. doi: 10.1038/bjc.2011.472 www.bjcancer.com Published online 10 November 2011 (C) 2011 Cancer Research UK

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Author(s): Schleiermacher G, Michon J, Ribeiro A, Pierron G, Mosseri V, Rubie H, Munzer C, Benard J, Auger N, Combaret V, Janoueix-Lerosey I, Pearson A, Tweddle DA, Bown N, Gerrard M, Wheeler K, Noguera R, Villamon E, Canete A, Castel V, Marques B, de Lacerda A, Tonini GP, 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

Publication type: Article

Publication status: Published

Journal: British Journal of Cancer

Year: 2011

Volume: 105

Issue: 12

Pages: 1940-1948

Print publication date: 01/11/2011

ISSN (print): 0007-0920

ISSN (electronic):

Publisher: Nature Publishing Group

URL: http://dx.doi.org/10.1038/bjc.2011.472

DOI: 10.1038/bjc.2011.472

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