Age-dependent accumulation of genomic aberrations and deregulation of cell cycle and telomerase genes in metastatic neuroblastoma
Coco, Simona; Theissen, Jessica; Scaruffi, Paola; Stigliani, Sara; Moretti, Stefano; Oberthuer, André; Valdora, Francesca; Fischer, Matthias; Gallo, Fabio; Hero, Barbara; Bonassi, Stefano; Berthold, Frank; Tonini, Gian Paolo (2012), Age-dependent accumulation of genomic aberrations and deregulation of cell cycle and telomerase genes in metastatic neuroblastoma, International Journal of Cancer, 131, 7, p. 1591-1600. 10.1002/ijc.27432
Type
Article accepté pour publication ou publiéDate
2012Journal name
International Journal of CancerVolume
131Number
7Publisher
Wiley
Pages
1591-1600
Publication identifier
Metadata
Show full item recordAuthor(s)
Coco, SimonaTheissen, Jessica
University of Cologne
Scaruffi, Paola
Department of Obstetrics and Gynecology
Stigliani, Sara
Moretti, Stefano

Laboratoire d'analyse et modélisation de systèmes pour l'aide à la décision [LAMSADE]
Oberthuer, André
University of Cologne
Valdora, Francesca
Fischer, Matthias
University of Cologne
Gallo, Fabio
Hero, Barbara
University of Cologne
Bonassi, Stefano
San Raffaele Pisana IRCCS
Berthold, Frank
University of Cologne
Tonini, Gian Paolo
Abstract (EN)
About 50% of children with neuroblastoma (NB) show a metastatic disease and have a poor prognosis. However, disease progression is greatly variable and depends on patients' age and MYCN oncogene amplification. To investigate the role of patients' age in tumor aggressiveness, we performed array-CGH and gene expression profiles of three groups (G) of metastatic NBs: G1, stage 4S patients and MYCN single copy (MYCN−) tumors; G2, stage 4 patients, ≤18 months of age, MYCN− tumors and favorable outcome and G3, Stage 4 patients, ≥19 months with unfavorable outcome. G1 was characterized by numerical aberrations prevalently; on the contrary, all G3 tumors had structural rearrangements, whereas G2 showed an intermediate pattern. The average of numerical alterations decreased significantly from G1 to G2 to G3 (p < 0.01). Contrarily, the number of structural aberrations increased from G1 to G2 to G3 (p < 2.35 E−05). Noteworthy, G3/MYCN− NBs were characterized by several complex intrachromosome rearrangements. Expression analysis of the three groups showed significant differences in genes of Rho and Ras signaling pathways, development and adhesion, cell cycle regulation and telomerase activity. Accumulation of structural alterations increased with patients' age and was associated with a more aggressive disease. Abnormal expression of genes involved in cell cycle and telomerase in G3 may be responsible for the genomic instability in this cohort of patients. The higher DNA instability observed in G3/MYCN− NBs than in MYCN-amplified G3 may also explain why patients ≥19 months have a poor outcome independently by MYCN status.Subjects / Keywords
chromosome instability; CGH; microarray; metastatic tumor; neuroblastomaRelated items
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