Specific gene expression profiles and chromosomal abnormalities are associated with infant disseminated neuroblastoma

Thirty-five NB tumours from patients diagnosed at < 18 months (25 stage 4 and 10 stage 4s), were evaluated by allelic and gene expression analyses.All stage 4s patients underwent spontaneous remission, only 48% stage 4 patients survived despite combined modality therapy. Stage 4 tumours were 90% near-diploid/tetraploid, 44% MYCN amplified, 77% had 1p LOH (50% 1p36), 23% 11q and/or 14q LOH (27%) and 47% had 17q gain. Stage 4s were 90% near-triploid, none MYCN amplified and LOH was restricted to 11q. Initial comparison analyses between stage 4s and 4 < 12 months tumours revealed distinct gene expression profiles. A significant portion of genes mapped to chromosome 1 (P < 0.0001), 90% with higher expression in stage 4s, and chromosome 11 (P = 0.0054), 91% with higher expression in stage 4. Less definite expression profiles were observed between stage 4s and 4 < 18m, yet, association with chromosomes 1 (P < 0.0001) and 11 (P = 0.005) was maintained. Distinct gene expression profiles but no significant association with specific chromosomal region localization was observed between stage 4s and stage 4 < 18 months without MYCN amplification.Specific chromosomal aberrations are associated with distinct gene expression profiles which characterize spontaneously regressing or aggressive infant NB, providing the biological basis for the distinct clinical behaviour.In 1971, a special and rare subgroup of metastatic NB affecting very young infants and characterized by a unique pattern of dissemination and a high incidence of spontaneous regression was described [1]. This subgroup, designated stage 4s (s for special), has been recognized as a distinct clinical entity in all subsequent classifications of NB [2].Historically, stage 4s is defined as a small primary tumour (usually resectable and not crossing the midline) in children <1 year of age, with no bony metastasis and minimal marrow involvement [2]. Conversely, infant stage 4 NB typically includes extensive marrow involvement