It assembly affect ribosome synthesis and activate a p53 response through a nucleolus mediated stress. Nucleolus is the major site of ribosome production and it has been shown that disruption of the nucleolus is required for p53 activation and stabilization. We report here that a deficiency in L11 activates the p53 pathway, and absence of L11 disrupts the normal embryonic development of zebrafish, presumably through a p53-mediated apoptotic response. The described FGFR1 and FGFR2 mutations occur outside the kinase domain, but in identical positions to activating germline mutations known to predispose to skeletal dysplasias. Other FGFR gene alterations have also been reported in human cancers, although rarely in exons encoding the kinase domain. Previously we reported that the level of the mouse wild-type p53 protein was reduced in 10 of 10 tumor samples as compared to matched normal lung tissue of the transgenic mouse. Hence, these patients might represent patients with early symptoms of MS. In addition, several of these investigators have noted gene transcription of messenger RNA by C. pneumoniae in CSF from MS patients suggesting active VE-821 infection by this pathogen.The reduction in the level of murine wildtype p53 protein may be associated with overexpression of p53 ubiquitin–protein ligase Pirh2 and the “dominant-negative” effect of the mutant p53. One copy of the wild type p53 is sufficient to cause cell cycle arrest post irradiation , which may explain the delay in tumor development in our transgenic animals with the two murine wildtype p53 alleles in addition to the human mutant. This would also suggests that the p53 has a weak dominant-negative effect. Previous in vitro studies support this notion. At the age of 13–21 months, when additional genetic and epigenetic alterations are able to combine with the mutant p53, a significant difference in tumor formation between the transgenic and the nontransgenic mice would then be appreciated. We plan to characterize the functional consequences of the two reported FGFR4 mutations and determine their prevalence in independent lung and other tumor specimen banks. This study has some potential limitations. First, we examined only 39 genes. We did not sequence all related gene family members such as RPS6KA1-6, MAP2K3, and MAP2K7. This study also did not seek potential mutations in genes encoding adaptor proteins or phosphatases that might affect the ERBB signaling pathway. Second, WGA could have skewed the results by selectively amplifying DNA from normal rather than tumor tissue. However, evaluation of data from multiple assays has established that base-calling discrepancies between amplified and unamplified samples are minimal and not significantly different than that observed after re-sequencing non-amplified samples. Consistent with this, in all cases where we found an EGFR or KRAS mutation in the original non-WGA-treated sample, we also detected the same mutation in the corresponding WGA-treated sample.