MYCN-non-amplified metastatic neuroblastoma with good prognosis and spontaneous regression: a molecular portrait of stage 4S.
Stage 4 neuroblastoma (NB) are heterogeneous regarding their clinical presentations and behavior. Indeed infants (stage 4S and non-stage 4S of age <365days at diagnosis) show regression contrasting with progression in children (>365days). Our study aimed at: (i) identifying age-based genomic and gene expression profiles of stage 4 NB supporting this clinical stratification; and (ii) finding a stage 4S NB signature. Differential genome and transcriptome analyses of a learning set of MYCN-non amplified stage 4 NB tumors at diagnosis (n=29 tumors including 12 stage 4S) were performed using 1Mb BAC microarrays and Agilent 22K probes oligo-microarrays. mRNA chips data following filtering yielded informative genes before supervised hierarchical clustering to identify relationship among tumor samples. After confirmation by quantitative RT-PCR, a stage 4S NB's gene cluster was obtained and submitted to a validation set (n=22 tumors). Genomic abnormalities of infant's tumors (whole chromosomes gains or loss) differ radically from that of children (intra-chromosomal rearrangements) but could not discriminate infants with 4S from those without this presentation. In contrast, differential gene expression by looking at both individual genes and whole biological pathways leads to a molecular stage 4S NB portrait which provides new biological clues about this fascinating entity.
Bénard
Jean
J
Molecular Interactions in Cancer CNRS-UMR 8126, IFR54, Institut Gustave Roussy, 39, rue C. Desmoulins, Villejuif 94805 Cedex, France. benard@igr.fr
Raguénez
Gilda
G
Kauffmann
Audrey
A
Valent
Alexander
A
Ripoche
Hugues
H
Joulin
Virginie
V
Job
Bastien
B
Danglot
Gisèle
G
Cantais
Sabrina
S
Robert
Thomas
T
Terrier-Lacombe
Marie-José
MJ
Chassevent
Agnès
A
Koscielny
Serge
S
Fischer
Matthias
M
Berthold
Frank
F
Lipinski
Marc
M
Tursz
Thomas
T
Dessen
Philippe
P
Lazar
Vladimir
V
Valteau-Couanet
Dominique
D
D000367:Age Factors; D001185:Artificial Intelligence; D002675:Child, Preschool; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D023281:Genomics; D006801:Humans; D007223:Infant; D008297:Male; D025202:Molecular Diagnostic Techniques; D000071447:N-Myc Proto-Oncogene Protein; D009362:Neoplasm Metastasis / Q000235:genetics* / Q000473:pathology; D009447:Neuroblastoma / Q000235:genetics* / Q000473:pathology*; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D011379:Prognosis; D012075:Remission, Spontaneous
C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins