Genetics and Genomics

British Journal of Cancer (2007) 97, 238–246. doi:10.1038/sj.bjc.6603820 www.bjcancer.com
Published online 19 June 2007

Chromosomal CGH identifies patients with a higher risk of relapse in neuroblastoma without MYCN amplification

G Schleiermacher1,2, J Michon2, I Huon3, C Dubois d'Enghien3, J Klijanienko4, H Brisse5, A Ribeiro3, V Mosseri6, H Rubie7, C Munzer7, C Thomas8, D Valteau-Couanet9, A Auvrignon10, D Plantaz11, O Delattre1 and J Couturier1,3 on behalf of the Société Française des Cancers de l'Enfant (SFCE)

  1. 1INSERM U830, Institut Curie, Paris, France
  2. 2Département d'Oncologie Pédiatrique, Institut Curie, Paris, France
  3. 3Service de Génétique Oncologique, Institut Curie, Paris, France
  4. 4Service de Pathologie, Institut Curie, Paris, France
  5. 5Département d'Imagerie Médicale, Institut Curie, Paris, France
  6. 6Service de Biostatistique, Institut Curie, Paris, France
  7. 7Unité d'Hemato-Oncologie, Hôpital des Enfants, Toulouse, France
  8. 8Unité d'Onco-Hématologie Pédiatrique, Hôpital de la Mère et de l'Enfant- CHU de Nantes, Nantes, France
  9. 9Département de Pédiatrie, Institut Gustave-Roussy, Villejuif, France
  10. 10Service d'Hématologie et d'Oncologie Pédiatrique, Hôpital Trousseau, Paris, France
  11. 11Département de Pédiatrie, CHU, Grenoble, France

Correspondence: Dr G Schleiermacher, Département d'Oncologie Pédiatrique, Institut Curie, 26 rue d'Ulm, 75248 Paris Cedex 05, France. E-mail: gudrun.schleiermacher@curie.net

Received 31 January 2007; Revised 30 April 2007; Accepted 1 May 2007; Published online 19 June 2007.

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Abstract

Whereas neuroblastoma (NB) with MYCN amplification presents a poor prognosis, no single marker allows to reliably predict outcome in tumours without MYCN amplification. We report here an extensive analysis of 147 NB samples at diagnosis, without MYCN amplification, by chromosomal comparative genomic hybridisation (CGH), providing a comprehensive overview of their genomic imbalances. Comparative genomic hybridisation profiles showed gains or losses of entire chromosomes (type 1) in 71 cases, whereas partial chromosome gains or losses (type 2), including gain involving 17q were observed in 68 cases. Atypical profiles were present in eight cases. A type 1 profile was observed more frequently in localised disease (P<0.0001), and in patients of less than 12 months at diagnosis (P<0.0001). A type 2 genomic profile was associated with a higher risk of relapse in the overall population (log-rank test; P<0.0001), but also in the subgroup of patients with localised disease (log-rank test, P=0.007). In multivariate analysis, the genomic profile was the strongest independent prognostic factor. In conclusion, the genomic profile is of prognostic impact in patients without MYCN amplification, making it a help in the management of low-stage NB. Further studies using higher-resolution CGH are needed to better characterise atypical genomic alterations.

Keywords:

neuroblastoma, pangenomic analysis, CGH, prognosis