Journal
BRITISH JOURNAL OF CANCER
Volume 105, Issue 12, Pages 1940-1948Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/bjc.2011.472
Keywords
neuroblastoma; infants; genomic profile; segmental chromosome alterations; prognosis
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Funding
- Institut National de la Sante et de la Recherche Medicale
- Ligue Nationale Contre le Cancer (Equipe labellisee)
- PHRC [AOM 02014]
- Ligue Nationale Contre le Cancer
- RTICC [RD06/0020/0102]
- ISCIII
- ERDF
- FAECC [396/2009]
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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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