To the editor—Neuroblastoma (NB) is a tumor of infancy that presents a high rate of spontaneous regression, a phenomenon that likely reflects the activation of an apoptotic and/or differentiation program. An attractive hypothesis suggested that the caspase-8 gene (CASP8), which encodes a key enzyme at the top of the apoptotic cascade, is an anti-oncogene that can be inactivated by methylation or deletion in MYCN-amplified neuroblastoma1. However, subsequent reports have not fully confirmed this model of NB development2, 3. To clarify this question, we have studied CASP8 expression in primary tumors and NB cell lines and its relationship to CpG methylation at the putative 5′ regulatory region of the gene. Reverse transcription-PCR and western-blot analyses showed minimal or absent expression of CASP8 in 5 of 11 cell lines and in 6 of 31 NB samples (19 MYCN-single copy and 12 MYCN-amplified). As in other reports2, 3, we did not observe a defined correlation between CASP8 silencing and MYCN amplification (Fig. 1a). However, the role of