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Could bladder cells shed into urine be used to indicate risk of developing cancer in remote organs using Next Generation Sequencing? A focused, mixed methods review.

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Background: Dysplasia in the bladder can be a precursor to cancer and dysplastic cells are potentially detectable in voided urine. Changes in the healthy bladder epithelium have been described as ‘field cancerization’. Urine offers a non-invasive way to monitor the accumulation of mutations in the dysplastic bladder epithelium. Genetic mutational signatures would be one way of characterizing dysplasia and potentially indicate environmental exposure and cancer risk if they could be derived from bladder cells collected from urine. Other dysplastic tissues are already monitored in detection strategies as part of cancer screening.

Aim & Methods: Part A: A literature review comprising a focused systematic search of the literature to answer the question, ‘What studies have successfully sequenced DNA from voided urine and what were the genomic outputs?’ Part B: The curation and analysis of the Signal dataset to identify mutational signatures that are common to tumours of the bladder and other organs.

Results: Studies have successfully sequenced bladder lining cells from voided urine with deep or ultra-deep next generation sequencing from panels of targeted genes. To date, no studies have sought to derive mutational signatures from bladder cells from voided urine. Analysis of the Signal dataset reveals multiple shared signatures between tumours of the bladder and other organs including two in the APOBEC pathway and two with Mismatch Repair involvement. Organs, the tumours of which the bladder commonly shares a signature with include the liver, lung, prostate, pancreas and kidney.

Conclusion: The sequencing of urine cell pellets is feasible for the detection of mutational signatures and mutational signatures found in bladder tumours are common in other organs. Experimentation may reveal ways in which shared signatures, if detected in the bladder, could inform risk and screening in a public health and early detection setting of remote organs which share the same signature.



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