Abstractp53 mutations have been reported in cell lines derived from relapsed neuroblastoma tumors. We hypothesize that functional inactivation of p53 by mutation or other mechanisms is common in relapsed neuroblastoma and can contribute to chemoresistance. Our aim was to determine the frequency of p53 mutations, p14ARF methylation, or deletion and MDM2 amplification in 23 neuroblastoma cell lines (6 derived at diagnosis and 17 derived at relapse). One cell line was p53 mutant (BE2c) and two cell lines were deleted for p14 ARF (LAN-6 and SHEP). Two cell lines were methylated for p14ARF (GIMEN and PER-108), one of which had low levels of p14 ARF mRNA expression which increased following demethylation with 5-aza-2/deoxycytidine treatment (GIMEN), and four cell lines were confirmed to be MDM2-amplified. All these cell lines were derived from neuroblastomas at relapse. Inactivation of the p53 pathway was observed in 9 out of 17 neuroblastoma cell lines (53%) established at relapse and in none of the cell lines established from pretreatment tumors. If these data are confirmed in neuroblastoma tumors, this suggests that p53-independent therapy and reactivation of inactive p53 approaches would be useful in the management of relapsed neuroblastoma. (Cancer Res 2006; 66(4): 2138-45)

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Changes in gene expression induced by salinity were investigated in a suspension culture of the tropieal, graminaceous plant sugarcane {Saeeharum spp,). Three cell lines tolerant to 5, 10 and 15kg m"-' NaCl were adapted and the expression of newly synthesized proteins and translatable mRNAs in these cell lines were compared with those in unadapted cells on highresolution, two-dimensional gels. Specific proteins and mRNAs alteted by salinity were identified. At the protein level, the expression of 15 proteins was induced or enhanced, and that of three others was lepressed or abolished. At the translatable mRNA level, the expression of 18 mRNAs was induced or enhanced, and that of eight others was repressed or abolished. The expression of some of these was also regulated, depending on the salt-adapted cell line. The above changes were characteristic of salt-adapted cells and were not found in unadapted cells undergoing a short-term salt stress. Overall, 29 sugarcane proteins were regulated by salinity: for 15, translatable mRNAs were found; for three, no translatable mRNA was detected; and for six of the remaining 11, in vivo equivalents were not observed. These data suggest that a multitude of mechanistns at the transcriptional, post-transcriptional and post-translational levels tnay contribute to the control of gene expression in the salt-adapted sugarcane cells.