Association of Plasma and Urinary Mutant DNA with Clinical Outcomes in Muscle Invasive Bladder Cancer

K. M. Patel, K. E. Van Der Vos, Christopher G Smith, F. Mouliere, D. Tsui, James A 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

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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-A nd 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.

Original languageEnglish
Article number5554
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - 1 Dec 2017

Cite this

Patel, K. M., Van Der Vos, K. E., Smith, C. G., Mouliere, F., Tsui, D., Morris, J. A., ... Van Der Heijden, M. S. (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