|Budget Amount *help
¥6,500,000 (Direct Cost : ¥6,500,000)
Fiscal Year 1995 : ¥900,000 (Direct Cost : ¥900,000)
Fiscal Year 1994 : ¥5,600,000 (Direct Cost : ¥5,600,000)
To study natural of reuroblastoma, we analyzed tumor clonality in terms of DNA content, N-myc gene amplification and deletion of the short arm of chromosome 1(1p). Intratumor clonal heterogeneity was revealed in several cases, indicating two evidences for clonal evolution in neuroblastoma. Firstly, interphase FISH revealed the coexistence of clones with and without N-myc amplification and/or deletion in a primary tumor. This result suggests that the generation of subclone with N-myc amplification or 1p deletion occurred within the same tumor. Furthermore, in this case, all metastatic foci consisted of homogeneous clones with N-myc amplification and 1p deletion, suggesting that the accumulation of these genetic changes results in their higher potential to metastasize and growth advantage. Therefore, the concept of multiple-step process of tumor progression could be applied to neuroblastoma. Secondly, DNA content delected by cytofluorometry revealed the coexistence of near-triploid and diploid clones in several tumors. This result is of great significance, suggesting the probability that a part of favorable tumors could evolve into unfavorable tumors. Since a part near-triploid clones can be derived, through a process of tetraploidization and/or non-disjunction of chromosomes, from diploid clone with genetic aberrations, we need to analyze more tumor samples before making a conclusion.