Association Of Plasma And Urinary Mutant DNA With Clinical Outcomes In Muscle Invasive Bladder Cancer
van der Vos, KE
van den Broek, D
van Rhijn, BW
van der Heijden, MS
Nature Publishing Group
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Patel, K., van der Vos, K., Smith, C., Mouliere, F., Tsui, D., Morris, J., Chandrananda, S., et al. (2017). Association Of Plasma And Urinary Mutant DNA With Clinical Outcomes In Muscle Invasive Bladder Cancer. Scientific Reports, 7 (1. 5554)https://doi.org/10.1038/s41598-017-05623-3
Muscle Invasive Bladder Cancer (MIBC) has a poor prognosis. Whilst patients can achieve a 6% improvement in overall survival with Neo-Adjuvant Chemotherapy (NAC), many do not respond. Body fluid mutant DNA (mutDNA) may allow non-invasive identification of treatment failure. We collected 248 liquid biopsy samples including plasma, cell pellet (UCP) and supernatant (USN) from spun urine, from 17 patients undergoing NAC. We assessed single nucleotide variants and copy number alterations in mutDNA using Tagged-Amplicon- and shallow Whole Genome- Sequencing. MutDNA was detected in 35.3%, 47.1% and 52.9% of pre-NAC plasma, UCP and USN samples respectively, and urine samples contained higher levels of mutDNA (p = <0.001). Longitudinal mutDNA demonstrated tumour evolution under the selective pressure of NAC e.g. in one case, urine analysis tracked two distinct clones with contrasting treatment sensitivity. Of note, persistence of mutDNA detection during NAC predicted disease recurrence (p = 0.003), emphasising its potential as an early biomarker for chemotherapy response.
We would like to thank the CRUK-CI core facilities in particular; the bio-repository, genomic and bioinformatic cores. We are grateful for support from Cancer Research UK, the University of Cambridge and the Netherlands Cancer Institute. CGS and CEM were supported by European Research Council . KP was supported by the Cambridge Cancer Centre [A18345], the Royal College of Surgeons of England [KEVAL PATEL] and the Addenbrookes Charitable Trust [28/13A 9935]. MSH was supported by a grant from the Netherlands Organization for Scientific Research (NWO, Veni program).
European Research Council (337905)
Cancer Research UK (C14303_do not transfer)
Cancer Research UK (C48525/A18345)
External DOI: https://doi.org/10.1038/s41598-017-05623-3
This record's URL: https://www.repository.cam.ac.uk/handle/1810/266751