Wellcome Trust Centre For Mitochondrial Research

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In this week’s WCMR ‘Research in Progress’ meeting, we heard from 2nd year PhD student Nana-Jane Chipampe who works between the WCMR and Northern Institute for Cancer Research and is funded by the NIHR Newcastle Biomedical Research Centre at Newcastle University. Nana-Jane talked about her research project that is investigating urinary mitochondrial DNA mutations as naturally occurring tumour “barcodes” to trace bladder cancer recurrence. Here, Nana-Jane tells us why this is important.

Although we take bladder function for granted, ageing can result in lower urinary tract problems for many individuals across the world. There is also a risk of malignant transformation. Importantly, bladder cancer is the seventh most common cancer in both men and women in the UK.

The major clinical problem of bladder cancer is the 40% risk of recurrence within 3 years. This high recurrence rate is known to reflect incomplete removal of the tumour during resection.

Mitochondrial DNA – a unique translational opportunity

During ageing, mitochondrial DNA (mtDNA) accumulates mutations that can lead to disease. This process has not been studied in detail within the human bladder, where functional and cancerous changes are common as we get older.

Urinary cell-free mtDNA – potential bladder cancer biomarker

Tumour cells are shed readily into urine, meaning that a urine sample could be used for non-invasive testing to detect bladder cancer recurrence. For this to be possible, we need to identify a tumour biomarker, or “barcode”, that could be used to detect tumour cells within the urine sample.

There are currently no bladder urinary biomarkers in routine clinical use that could be used to detect tumour cells. It has been shown, however, that mtDNA mutations are common in non-muscle invasive bladder cancer. These mutations are tumour-specific and absent from cells in the patient’s normal bladder lining.  This means that urinary mtDNA mutations could be used as naturally occurring “barcodes” to detect bladder cancer recurrence.

The use of urinary mtDNA as a biomarker would transform clinical practice by confirming bladder cancer recurrence and reducing the need for surveillance cystoscopy. Longer term, urinary mtDNA analysis could also be used to ensure complete tumour removal and provide the first non-invasive detection of early bladder cancer recurrence.

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