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| Status |
Public on Oct 05, 2012 |
| Title |
High-resolution, genome-wide analysis of human metastatic neuroblastoma samples by array-Comparative Genomic Hybridization (aCGH) |
| Organism |
Homo sapiens |
| Experiment type |
Genome variation profiling by array
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| Summary |
Less than 30% of children with high-risk (HR) metastatic neuroblastoma (NB) show a long survival (Pearson 2000). In order to identify novel molecular prognostic markers useful to better predict patients’ relapse risk estimation, we performed genome- and/or transcriptome-wide analyses of 129 stage 4 HR-NBs. This is the largest study for this NB subtype. Children older than 1 year of age at diagnosis were categorized as “short-survivors” (dead of disease within 5 years from diagnosis) and “long-survivors” (alive with an overall survival time > 5 years). A significant correlation of patient survival with the presence of small number of segmental copy number aberrations (CNA < 3) was observed. Thus, within the group of stage 4 HR-NBs, we identified a specific subgroup of patients (those with highest number of CNA) that have a higher risk of progression/recurrence. The complex genomic pattern is an independent prognostic marker, since MYCN oncogene amplification only affects the predictive value of single CNA (i.e., 1p loss, 17q gain). Integrative analysis of genomic and expression signatures demonstrated that fatal outcome is associated with loss of cell cycle control and with progression of tumor due to deregulation of Rho GTPase signaling and genes related to cell motility. Tumors with MYCN amplification showed a lower chromosome instability compared to MYCN-single copy NBs (P=0.0008), dominated by 17q gain and 1p loss. Moreover, our results suggest that the MYCN amplification mainly drives the disruption of neuronal differentiation and the reduction of cell adhesion process involved in tumor invasion and metastasis.
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| Overall design |
For array-CGH profiling, we analyzed 91 samples of metastatic neuroblastomas. All patients were classified as stage 4 and they were older than 1 year of age at time of diagnosis. Regarding the clinical course, 46 were short-survivors (dead of disease within 60 months from diagnosis. Deaths due to toxicity were censored) and 45 were long-survivors (alive with an overall survival time > 60 months). This submission consists of 22 new samples and 69 other cases previously deposited in GEO under Series accessions GSE14109 and GSE25771.
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| Contributor(s) |
Scaruffi P, Theissen J, Coco S, Stigliani S |
| Citation(s) |
23019414 |
| Submission date |
Feb 21, 2012 |
| Last update date |
Dec 06, 2012 |
| Contact name |
PAOLA SCARUFFI |
| E-mail(s) |
paola.scaruffi@hsanmartino.it
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| Organization name |
"San Martino" Hospital
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| Lab |
Center of Physiopathology of Human Reproduction
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| Street address |
LARGO R. BENZI, 10
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| City |
Genova |
| State/province |
GE |
| ZIP/Postal code |
16132 |
| Country |
Italy |
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| Platforms (2) |
| GPL2873 |
Agilent-012750 Human Genome CGH Microarray 44A (Feature number version) |
| GPL5477 |
Agilent-014950 Human Genome CGH Microarray 4x44K (Feature Number version) |
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| Samples (35)
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| Relations |
| BioProject |
PRJNA151989 |
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