There is evidence that carcinoma in situ (CIS) is the precursor of invasive urothelial carcinoma, a tumour characterized by frequent gene promoter methylation. The timing of altered DNA methylation is unknown in this pathway. Here we investigate gene methylation in 196 consecutive samples of normal urothelium, CIS, and tumours from 104 patients with both CIS and invasive urothelial carcinoma using quantitative methyl-sensitive polymerase chain reaction for six genes (p16, p14, E-cadherin, RARbeta2, RASSF1a, and GSTP1). Control normal urothelial samples from 15 patients with no history of urothelial carcinoma were also analysed. Immunohistochemistry established the expression of well-characterized CIS markers p53 and cytokeratin 20. Promoter methylation occurred frequently in both normal urothelium and CIS samples from patients with urothelial carcinoma, and increased with progression from normal to invasive urothelial carcinoma, at both specific loci (chi2 test: E-cadherin, p=0.0001; RASSF1a, p=0.003, RARbeta2, p=0.007, p16, p=0.024) and in general (methylation indices [t-test, p<0.0001]). Methylation was associated with cytokeratin 20 expression (t-test, p=0.004) and poor prognosis, and with increased progression to tumour death in patients whose CIS samples showed methylation, in comparison with those without methylation (log rank p<0.03). Promoter methylation occurs early in the urothelial carcinogenic pathway and appears to be a good biomarker of the invasive urothelial carcinoma phenotype.

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We report the draft genome of Brevundimonas diminuta strain XGC1, isolated from a tuberculosis-infected patient in Gujarat, India. This study also reveals that the B. diminuta XGC1 strain has acquired mutation to confer resistance to quinolone drugs.

Co-inheritance of sickle cell anemia and β-thalassemia traits require medical attention. Individuals with sickle cell and β-thalassemia disorders produce abnormal form of hemoglobin or decreased synthesis or complete absence of the β-globin chains of hemoglobin. Therefore, affected individuals might require blood transfusions at regular intervals. Prenatal diagnosis of fetal hemoglobinopathy should be offered when the fetus is at risk of being affected. The aim of this study was to assess the applicability of the nucleotide sequencing method in the identification of both diseases and to identify and counsel asymptomatic parents to make reproductive choices. We demonstrate the ability to detect these traits in a family, which was suspected to be carrying β-thalassemia mutations as per the clinician.

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