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

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...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0a5384dd632447b7bcf66a21c708202c
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spelling	oai:doaj.org-article:0a5384dd632447b7bcf66a21c708202c2021-12-02T12:30:12ZAssociation Of Plasma And Urinary Mutant DNA With Clinical Outcomes In Muscle Invasive Bladder Cancer10.1038/s41598-017-05623-32045-2322https://doaj.org/article/0a5384dd632447b7bcf66a21c708202c2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05623-3https://doaj.org/toc/2045-2322Abstract 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.K. M. PatelK. E. van der VosC. G. SmithF. MouliereD. TsuiJ. MorrisD. ChandranandaF. MarassD. van den BroekD. E. NealV. J. GnanapragasamT. ForshewB. W. van RhijnC. E. MassieN. RosenfeldM. S. van der HeijdenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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 Association Of Plasma And Urinary Mutant DNA With Clinical Outcomes In Muscle Invasive Bladder Cancer
description	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- 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.
format	article
author	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
author_facet	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
author_sort	K. M. Patel
title	Association Of Plasma And Urinary Mutant DNA With Clinical Outcomes In Muscle Invasive Bladder Cancer
title_short	Association Of Plasma And Urinary Mutant DNA With Clinical Outcomes In Muscle Invasive Bladder Cancer
title_full	Association Of Plasma And Urinary Mutant DNA With Clinical Outcomes In Muscle Invasive Bladder Cancer
title_fullStr	Association Of Plasma And Urinary Mutant DNA With Clinical Outcomes In Muscle Invasive Bladder Cancer
title_full_unstemmed	Association Of Plasma And Urinary Mutant DNA With Clinical Outcomes In Muscle Invasive Bladder Cancer
title_sort	association of plasma and urinary mutant dna with clinical outcomes in muscle invasive bladder cancer
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/0a5384dd632447b7bcf66a21c708202c
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Association Of Plasma And Urinary Mutant DNA With Clinical Outcomes In Muscle Invasive Bladder Cancer

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