Multiplex PCR and Next Generation Sequencing for the Non-Invasive Detection of Bladder Cancer

Highly sensitive and specific urine-based tests to detect either primary or recurrent bladder cancer have proved elusive to date. Our ever increasing knowledge of the genomic aberrations in bladder cancer should enable the development of such tests based on urinary DNA

Frequency of mutant <i>FGFR3</i> reads in urinary DNA.

<p>Individual patients are listed along the x-axis as indicated and the frequency of mutant reads at comic loci is shown for each individual.</p

Frequency of mutant <i>TERT</i> promoter reads in urinary DNA.

<p>The graph shows the percentage of mutant reads in each patient sample considering point mutations at positions chr5:1295228, chr5:1295242/1295243 and chr:1295250.</p

Childhood pneumonia, pleurisy and lung function: a cohort study from the first to sixth decade of life

Introduction: Adult spirometry following community-acquired childhood pneumonia has variably been reported as showing obstructive or non-obstructive deficits. We analysed associations between doctor-diagnosed childhood pneumonia/pleurisy and more comprehensive lung function in a middle-aged general population cohort born in 1961. Methods: Data were from the prospective population-based Tasmanian Longitudinal Health Study cohort. Analysed lung function was from ages 7 years (prebronchodilator spirometry only, n=7097), 45 years (postbronchodilator spirometry, carbon monoxide transfer factor and static lung volumes, n=1220) and 53 years (postbronchodilator spirometry and transfer factor, n=2485). Parent-recalled histories of doctor-diagnosed childhood pneumonia and/or pleurisy were recorded at age 7. Multivariable linear and logistic regression were used. Results: At age 7, compared with no episodes, childhood pneumonia/pleurisy-ever was associated with reduced FEV1:FVC for only those with current asthma (beta-coefficient or change in z-score=-0.20 SD, 95% CI -0.38 to -0.02, p=0.028, p interaction=0.036). At age 45, for all participants, childhood pneumonia/pleurisy-ever was associated with a restrictive pattern: OR 3.02 (1.5 to 6.0), p=0.002 for spirometric restriction (FVC less than the lower limit of normal plus FEV1:FVC greater than the lower limit of normal); total lung capacity z-score -0.26 SD (95% CI -0.38 to -0.13),

Patient demographics.

<p>NA: not applicable, NK: not known.</p

Confirmation of <i>TERT</i> mutations by Sanger sequencing.

<p>Panel A is a screenshot from IGV showing the proportion of mutant (green) and wt (brown) base calls for three urinary DNAs (surrounding wt sequence in grey). Sanger sequencing of the same three urinary DNAs is shown in panels B: sample 661 (chr5: 1,295,250 G>A), C: sample 857 (5: 1,295,228 G>A), and D: sample 576 (chr5: 1,242 & 243 G>A).</p

Occurrence of cosmic listed point mutations in urinary DNA from UBC patients.

<p>Each column represents an individual patient. Oncoprint representation generated at <a href="http://www.cbioportal.org/" target="_blank">http://www.cbioportal.org/</a>.</p