Chromosomal CGH identifies patients with a higher risk of relapse in neuroblastoma without MYCN amplification.
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.
Schleiermacher
G
G
INSERM U830, Institut Curie, Paris, France. gudrun.schleiermacher@curie.net
Michon
J
J
Huon
I
I
d'Enghien
C Dubois
CD
Klijanienko
J
J
Brisse
H
H
Ribeiro
A
A
Mosseri
V
V
Rubie
H
H
Munzer
C
C
Thomas
C
C
Valteau-Couanet
D
D
Auvrignon
A
A
Plantaz
D
D
Delattre
O
O
Couturier
J
J
D002877:Chromosomes, Human / Q000235:genetics; D005260:Female; D005784:Gene Amplification; D006801:Humans; D007223:Infant; D008297:Male; D000071447:N-Myc Proto-Oncogene Protein; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology*; D009447:Neuroblastoma / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics*; D009693:Nucleic Acid Hybridization; D015513:Oncogene Proteins / Q000235:genetics*; D012306:Risk; D016019:Survival Analysis
C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins