Association Of Plasma And Urinary Mutant DNA With Clinical Outcomes In Muscle Invasive Bladder Cancer

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.

Scientific reports. 2017 Jul 17*** epublish ***

K M Patel, K E van der Vos, C G Smith, F Mouliere, D Tsui, J Morris, D Chandrananda, F Marass, D van den Broek, D E Neal, V J Gnanapragasam, T Forshew, B W van Rhijn, C E Massie, N Rosenfeld, M S van der Heijden

Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge, CB2 0RE, UK., Division of Molecular Carcinogenesis, Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, 1066 CX, The Netherlands., Department of Clinical Chemistry, Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, 1066 CX, The Netherlands., Academic Urology Group, Department of Surgery & Oncology, University of Cambridge, Box 279 (S4), Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK., Department of Surgical Oncology (Urology), Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, 1066 CX, The Netherlands., Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge, CB2 0RE, UK. ., Division of Molecular Carcinogenesis, Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, 1066 CX, The Netherlands. .