Clinical characteristics and outcome of patients with neuroblastoma presenting genomic amplification of loci other than MYCN

• Published in: PloS one 2014-07, Vol.9 (7), p.e101990
• Main Authors: Guimier, Anne, Ferrand, Sandrine, Pierron, Gaëlle, Couturier, Jérôme, Janoueix-Lerosey, Isabelle, Combaret, Valérie, Mosseri, Véronique, Thebaud, Estelle, Gambart, Marion, Plantaz, Dominique, Marabelle, Aurélien, Coze, Carole, Rialland, Xavier, Fasola, Sylvie, Lapouble, Eve, Fréneaux, Paul, Peuchmaur, Michel, Michon, Jean, Delattre, Olivier, Schleiermacher, Gudrun
• Format: Article
• Language: English
• Subjects: Amplification; Cancer; Child, Preschool; Children; Chromosome 12; Chromosomes; Cloning; Comparative Genomic Hybridization; Cytogenetics; Ethics; Female; Gene Amplification - genetics; Histology; Humans; Hybridization; Infant; Kinases; Laboratories; Loci; Male; Medical diagnosis; Medical prognosis; Medicine and Health Sciences; Mutation; N-Myc Proto-Oncogene Protein; Neuroblastoma; Neuroblastoma - genetics; Nuclear Proteins - genetics; Oncogene Proteins - genetics; Pathogenesis; Patient outcomes; Patients; Retrospective Studies; Tumors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0101990

Somatically acquired genomic alterations with MYCN amplification (MNA) are key features of neuroblastoma (NB), the most common extra-cranial malignant tumour of childhood. Little is known about the frequency, clinical characteristics and outcome of NBs harbouring genomic amplification(s) distinct from MYCN. Genomic profiles of 1100 NBs from French centres studied by array-CGH were re-examined specifically to identify regional amplifications. Patients were included if amplifications distinct from the MYCN locus were seen. A subset of NBs treated at Institut Curie and harbouring MNA as determined by array-CGH without other amplification was also studied. Clinical and histology data were retrospectively collected. In total, 56 patients were included and categorised into 3 groups. Group 1 (n = 8) presented regional amplification(s) without MNA. Locus 12q13-14 was a recurrent amplified region (4/8 cases). This group was heterogeneous in terms of INSS stages, primary localisations and histology, with atypical clinical features. Group 2 (n = 26) had MNA as well as other regional amplifications. These patients shared clinical features of those of a group of NBs MYCN amplified (Group 3, n = 22). Overall survival for group 1 was better than that of groups 2 and 3 (5 year OS: 87.5%±11% vs 34.9%±7%, log-rank p