Novel risk stratification of patients with neuroblastoma by genomic signature, which is independent of molecular signature.
Oncogene
; 27(4): 441-9, 2008 Jan 17.
Article
en En
| MEDLINE
| ID: mdl-17637744
ABSTRACT
Human neuroblastoma remains enigmatic because it often shows spontaneous regression and aggressive growth. The prognosis of advanced stage of sporadic neuroblastomas is still poor. Here, we investigated whether genomic and molecular signatures could categorize new therapeutic risk groups in primary neuroblastomas. We conducted microarray-based comparative genomic hybridization (array-CGH) with a DNA chip carrying 2464 BAC clones to examine genomic aberrations of 236 neuroblastomas and used in-house cDNA microarrays for gene-expression profiling. Array-CGH demonstrated three major genomic groups of chromosomal aberrations silent (GGS), partial gains and/or losses (GGP) and whole gains and/or losses (GGW), which well corresponded with the patterns of chromosome 17 abnormalities. They were further classified into subgroups with different outcomes. In 112 sporadic neuroblastomas, MYCN amplification was frequent in GGS (22%) and GGP (53%) and caused serious outcomes in patients. Sporadic tumors with a single copy of MYCN showed the 5-year cumulative survival rates of 89% in GGS, 53% in GGP and 85% in GGW. Molecular signatures also segregated patients into the favorable and unfavorable prognosis groups (P=0.001). Both univariate and multivariate analyses revealed that genomic and molecular signatures were mutually independent, powerful prognostic indicators. Thus, combined genomic and molecular signatures may categorize novel risk groups and confer new clues for allowing tailored or even individualized medicine to patients with neuroblastoma.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Análisis de Secuencia por Matrices de Oligonucleótidos
/
Perfilación de la Expresión Génica
/
Neuroblastoma
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Child
/
Child, preschool
/
Humans
/
Infant
/
Newborn
Idioma:
En
Revista:
Oncogene
Asunto de la revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Año:
2008
Tipo del documento:
Article
País de afiliación:
Japón