Open AccessMYCN‐non‐amplified metastatic neuroblastoma with good prognosis and spontaneous regression: A molecular portrait of stage 4S
Author(s) -
Bénard Jean,
Raguénez Gilda,
Kauffmann Audrey,
Valent Alexander,
Ripoche Hugues,
Joulin Virginie,
Job Bastien,
Danglot Gisèle,
Cantais Sabrina,
Robert Thomas,
Terrier-Lacombe Marie-José,
Chassevent Agnès,
Koscielny Serge,
Fischer Matthias,
Berthold Frank,
Lipinski Marc,
Tursz Thomas,
Dessen Philippe,
Lazar Vladimir,
Valteau-Couanet Dominique
Publication year - 2008
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1016/j.molonc.2008.07.002
Subject(s) - neuroblastoma , stage (stratigraphy) , biology , dna microarray , gene , gene expression profiling , gene expression , genetics , cancer research , computational biology , bioinformatics , paleontology , cell culture
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.