We previously reported a high incidence of loss of heterozygosity (LOH) on chromosome 2q33 in neuroblastoma (NB), observed in various types of human cancers including lung cancer, head and neck cancer and follicular thyroid carcinoma. To better elucidate the role of chromosome 20 aberrations in NE, we examined common allelic imbalance (AI) regions on chromosome 20 in 82 NE patients using 10 polymorphic microsatellite markers. AI on 20 was detected in 26 (32%) of 82 NE cases. There was a distinct common AI region between the D2S115 and D2S307 markers on 2q33, The distance between these markers was about 2.0 cM, Recently, the caspase 8 and caspase 10 genes, both of which encode cystein protease, were mapped to chromosome 2q33, Since the common AI region on 2q33 includes the caspase 8 and caspase 10 genes, the alterations of these genes were examined further. Absent or reduced expression of caspase 8 and caspase 10 were found in 19 (70%) of 27 and two (7%) of 27 NE cell lines by reverse transcription-polymerase chain reaction, respectively. A missense mutation was detected at codon 96, GCT (Alanine) to GTT (Valine), of the caspase 8 gene in one of the NE cell lines lacking caspase 8 expression. Thirteen (68%) of 19 cell lines lacking caspase 8 expression displayed methylation of the CpG island of the caspase 8 gene, whereas only one (13%) of eight cell lines with caspase 8 expression showed caspase 8 methylation (P=0.031), Furthermore, there was significant association between Al at 2q33 and loss of caspase 8 expression (P=0.026), These results indicated that there was a tumor suppressor gene in the common AI region on chromosome 2q33 involved in the pathogenesis of a subset of NE. It is possible that the caspase 8 gene is one of the candidate tumor suppressor genes for NE and inactivation of this gene plays an important role in the tumorigenesis of NE through mainly its methylation.