Schmitt-Hoffner F, van Rijn S, Toprak UH, et al. - Given neuroblastoma patients clinical results range from spontaneous tumor regression to fatality, thus, mechanisms that result in tumor progression are important to be understood, researchers herein demonstrate that Forkhead Box R2 (FOXR2) activation reveals a subset of neuroblastoma tumors with unfavorable result and also they inquired the mechanism how FOXR2 associates with poor outcome in patients. They examined three independent transcriptional datasets of 1030 primary neuroblastomas with complete clinical annotation. FOXR2 expression as well as low levels of MYCN mRNA were demonstrated by 9% of tumors, in three integrated neuroblastoma datasets. In FOXR2-expressing neuroblastoma cell lines, it was found that FOXR2 knockdown caused cell cycle arrest, decreased cell growth, cell death, and decreased MYCN protein levels, all suggesting that FOXR2 is crucial for these tumors. It was concluded that FOXR2-induced MYCN stabilization is an alternative mechanism to MYCN amplification to elevate MYCN protein levels. As such, another subset of neuroblastoma patients with unfavorable clinical results was identified by FOXR2 expression.