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Background  Segmental genomic copy number alterations, such as loss of 11q or 3p and gain of 17q, are well established markers of poor outcome in neuroblastoma, and have been suggested to comprise tumor suppressor genes or oncogenes, respectively. The gene  forkhead box P1  ( FOXP1 ) maps to chromosome 3p14.1, a tumor suppressor locus deleted in many human cancers including neuroblastoma. FoxP1 belongs to a family of winged-helix transcription factors that are involved in processes of cellular proliferation, differentiation and neoplastic transformation.    Methods  Microarray expression profiles of 476 neuroblastoma specimens were generated and genes differentially expressed between favorable and unfavorable neuroblastoma were identified.  FOXP1  expression was correlated to clinical markers and patient outcome. To determine whether hypermethylation is involved in silencing of  FOXP1 , methylation analysis of the 5′ region of  FOXP1  in 47 neuroblastomas was performed. Furthermore,  FOXP1  was re-expressed in three neuroblastoma cell lines to study the effect of  FOXP1  on growth characteristics of neuroblastoma cells.    Results  Low expression of  FOXP1  is associated with markers of unfavorable prognosis like stage 4, age >18 months and  MYCN  amplification and unfavorable gene expression-based classification ( P  < 0.001 each). Moreover,  FOXP1  expression predicts patient outcome accurately and independently from well-established prognostic markers. Array-based CGH analysis of 159 neuroblastomas revealed that heterozygous loss of the  FOXP1  locus was a rare event (n = 4), but if present, was associated with low  FOXP1  expression. By contrast, DNA methylation analysis in 47 neuroblastomas indicated that hypermethylation is not regularly involved in  FOXP1  gene silencing. Re-expression of FoxP1 significantly impaired cell proliferation, viability and colony formation in soft agar. Furthermore, induction of  FOXP1  expression led to cell cycle arrest and apoptotic cell death of neuroblastoma cells.    Conclusions  Our results suggest that down-regulation of  FOXP1  expression is a common event in high-risk neuroblastoma pathogenesis and may contribute to tumor progression and unfavorable patient outcome.    Electronic supplementary material  The online version of this article (doi:10.1186/1471-2407-14-840) contains supplementary material, which is available to authorized users.

FOXP1inhibits cell growth and attenuates tumorigenicity of neuroblastoma