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Longitudinal analysis of individual cfDNA methylome patterns in metastatic prostate cancer

BACKGROUND: Disease progression and therapeutic resistance are hallmarks of advanced stage prostate cancer (PCa), which remains a major cause of cancer-related mortality around the world. Longitudinal studies, coupled with the use of liquid biopsies, offer a potentially new and minimally invasive pl...

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Autores principales: Silva, Romina, Moran, Bruce, Baird, Anne-Marie, O’Rourke, Colm J., Finn, Stephen P., McDermott, Ray, Watson, William, Gallagher, William M., Brennan, Donal J., Perry, Antoinette S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8403420/
https://www.ncbi.nlm.nih.gov/pubmed/34454584
http://dx.doi.org/10.1186/s13148-021-01155-w
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author Silva, Romina
Moran, Bruce
Baird, Anne-Marie
O’Rourke, Colm J.
Finn, Stephen P.
McDermott, Ray
Watson, William
Gallagher, William M.
Brennan, Donal J.
Perry, Antoinette S.
author_facet Silva, Romina
Moran, Bruce
Baird, Anne-Marie
O’Rourke, Colm J.
Finn, Stephen P.
McDermott, Ray
Watson, William
Gallagher, William M.
Brennan, Donal J.
Perry, Antoinette S.
author_sort Silva, Romina
collection PubMed
description BACKGROUND: Disease progression and therapeutic resistance are hallmarks of advanced stage prostate cancer (PCa), which remains a major cause of cancer-related mortality around the world. Longitudinal studies, coupled with the use of liquid biopsies, offer a potentially new and minimally invasive platform to study the dynamics of tumour progression. Our aim was to investigate the dynamics of personal DNA methylomic profiles of metastatic PCa (mPCa) patients, during disease progression and therapy administration. RESULTS: Forty-eight plasma samples from 9 mPCa patients were collected, longitudinally, over 13–21 months. After circulating cell-free DNA (cfDNA) isolation, DNA methylation was profiled using the Infinium MethylationEPIC BeadChip. The top 5% most variable probes across time, within each individual, were utilised to study dynamic methylation patterns during disease progression and therapeutic response. Statistical testing was carried out to identify differentially methylated genes (DMGs) in cfDNA, which were subsequently validated in two independent mPCa (cfDNA and FFPE tissue) cohorts. Individual cfDNA global methylation patterns were temporally stable throughout the disease course. However, a proportion of CpG sites presented a dynamic temporal pattern that was consistent with clinical events, including different therapies, and were prominently associated with genes linked to immune response pathways. Additionally, study of the tumour fraction of cfDNA identified > 2000 DMGs with dynamic methylation patterns. CONCLUSIONS: Longitudinal assessment of cfDNA methylation in mPCa patients unveiled dynamic patterns associated with disease progression and therapy administration, thus highlighting the potential of using liquid biopsies to study PCa evolution at a methylomic level. [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13148-021-01155-w.
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spelling pubmed-84034202021-08-30 Longitudinal analysis of individual cfDNA methylome patterns in metastatic prostate cancer Silva, Romina Moran, Bruce Baird, Anne-Marie O’Rourke, Colm J. Finn, Stephen P. McDermott, Ray Watson, William Gallagher, William M. Brennan, Donal J. Perry, Antoinette S. Clin Epigenetics Research BACKGROUND: Disease progression and therapeutic resistance are hallmarks of advanced stage prostate cancer (PCa), which remains a major cause of cancer-related mortality around the world. Longitudinal studies, coupled with the use of liquid biopsies, offer a potentially new and minimally invasive platform to study the dynamics of tumour progression. Our aim was to investigate the dynamics of personal DNA methylomic profiles of metastatic PCa (mPCa) patients, during disease progression and therapy administration. RESULTS: Forty-eight plasma samples from 9 mPCa patients were collected, longitudinally, over 13–21 months. After circulating cell-free DNA (cfDNA) isolation, DNA methylation was profiled using the Infinium MethylationEPIC BeadChip. The top 5% most variable probes across time, within each individual, were utilised to study dynamic methylation patterns during disease progression and therapeutic response. Statistical testing was carried out to identify differentially methylated genes (DMGs) in cfDNA, which were subsequently validated in two independent mPCa (cfDNA and FFPE tissue) cohorts. Individual cfDNA global methylation patterns were temporally stable throughout the disease course. However, a proportion of CpG sites presented a dynamic temporal pattern that was consistent with clinical events, including different therapies, and were prominently associated with genes linked to immune response pathways. Additionally, study of the tumour fraction of cfDNA identified > 2000 DMGs with dynamic methylation patterns. CONCLUSIONS: Longitudinal assessment of cfDNA methylation in mPCa patients unveiled dynamic patterns associated with disease progression and therapy administration, thus highlighting the potential of using liquid biopsies to study PCa evolution at a methylomic level. [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13148-021-01155-w. BioMed Central 2021-08-28 /pmc/articles/PMC8403420/ /pubmed/34454584 http://dx.doi.org/10.1186/s13148-021-01155-w Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Silva, Romina
Moran, Bruce
Baird, Anne-Marie
O’Rourke, Colm J.
Finn, Stephen P.
McDermott, Ray
Watson, William
Gallagher, William M.
Brennan, Donal J.
Perry, Antoinette S.
Longitudinal analysis of individual cfDNA methylome patterns in metastatic prostate cancer
title Longitudinal analysis of individual cfDNA methylome patterns in metastatic prostate cancer
title_full Longitudinal analysis of individual cfDNA methylome patterns in metastatic prostate cancer
title_fullStr Longitudinal analysis of individual cfDNA methylome patterns in metastatic prostate cancer
title_full_unstemmed Longitudinal analysis of individual cfDNA methylome patterns in metastatic prostate cancer
title_short Longitudinal analysis of individual cfDNA methylome patterns in metastatic prostate cancer
title_sort longitudinal analysis of individual cfdna methylome patterns in metastatic prostate cancer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8403420/
https://www.ncbi.nlm.nih.gov/pubmed/34454584
http://dx.doi.org/10.1186/s13148-021-01155-w
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