The nucleotide sequence of cosmid B1790, carrying the Rif-Str regions of the Mycobacterium leprae chromosome, has been determined. Twelve open reading frames were identified in the 36716bp sequence, representing 40% of the coding capacity. Five ribosomal proteins, two elongation factors and the beta and beta' subunits of RNA polymerase have been characterized and two novel genes were found. One of these encodes a member of the so-called ABC family of ATP-binding proteins while the other appears to encode an enzyme involved in repairing genomic lesions caused by free radicals. This finding may well be significant as M. leprae, an intracellular pathogen, lives within macrophages.

Abstract. All p53 family members are expressed in several isoforms through alternative promoters and alternative splicing. However, the significance of these isoforms is not yet well understood in cholangiocarcinoma (CCA). In this study, we investigated the expression of p53, p63, p73 and their isoforms at the mRNA and protein levels in CCA. The overexpression of ∆133p53 was observed in the CCA cell lines and clinical specimens. Moreover, the high expression of ∆133p53/TAp53 correlated with short overall survival (p<0.001). Defective p53, including mutant and ∆Np53, was associated with poor prognosis (p<0.024). Multivariate analysis demonstrated that ∆133p53̸TAp53 and mutant p53 protein may be used as independent prognostic factors for CCA. To our knowledge, this is the first report of the use of ∆133p53̸TAp53 as a potential biomarker in CCA.

Background:Genetic changes have been widely reported in association with cholangiocarcinoma (CCA), while epigenetic changes are poorly characterised. We aimed to further evaluate CpG-island hypermethylation in CCA at candidate loci, which may have potential as diagnostic or prognostic biomarkers.Methods:We analysed methylation of 26 CpG-islands in 102 liver fluke related-CCA and 29 adjacent normal samples using methylation-specific PCR (MSP). Methylation of interest loci was confirmed using pyrosequencing and/or combined bisulfite restriction analysis, and protein expression by immunohistochemistry.Results:A number of CpG-islands (OPCML, SFRP1, HIC1, PTEN and DcR1) showed frequency of hypermethylation in >28% of CCA, but not adjacent normal tissues. The results showed that 91% of CCA were methylated in at least one CpG-island. The OPCML was the most frequently methylated locus (72.5%) and was more frequently methylated in less differentiated CCA. Patients with methylated DcR1 had significantly longer overall survival (Median; 41.7 vs 21.7 weeks, P=0.027). Low-protein expression was found in >70% of CCA with methylation of OPCML or DcR1.Conclusion:Aberrant hypermethylation of certain loci is a common event in liver fluke-related CCA and may potentially contribute to cholangiocarcinogenesis. The OPCML and DcR1 might serve as methylation biomarkers in CCA that can be readily examined by MSP.