BRCA1 promoter hypermethylation on circulating tumor DNA correlates with improved survival of patients with ovarian cancer

Methylation of the BRCA1 promoter is an epigenetic gene expression regulator and is frequently observed in ovarian cancer; however, conversion of methylation status is thought to drive disease recurrence. Therefore, longitudinal monitoring of methylation status by liquid biopsy in cell‐free DNA may...

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Autores principales:	Maha Elazezy, Katharina Prieske, Lan Kluwe, Leticia Oliveira‐Ferrer, Sven Peine, Volkmar Müller, Linn Woelber, Barbara Schmalfeldt, Klaus Pantel, Simon A. Joosse
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	BRCA1 ctDNA liquid biopsy MS‐qPCR Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/d5b14d9287144f21a36580691214ee91
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spelling	oai:doaj.org-article:d5b14d9287144f21a36580691214ee912021-12-02T10:31:06ZBRCA1 promoter hypermethylation on circulating tumor DNA correlates with improved survival of patients with ovarian cancer1878-02611574-789110.1002/1878-0261.13108https://doaj.org/article/d5b14d9287144f21a36580691214ee912021-12-01T00:00:00Zhttps://doi.org/10.1002/1878-0261.13108https://doaj.org/toc/1574-7891https://doaj.org/toc/1878-0261Methylation of the BRCA1 promoter is an epigenetic gene expression regulator and is frequently observed in ovarian cancer; however, conversion of methylation status is thought to drive disease recurrence. Therefore, longitudinal monitoring of methylation status by liquid biopsy in cell‐free DNA may be a predictive marker. In total, 135 plasma samples were collected from 69 ovarian cancer patients before and during systemic treatment. Our liquid biopsy assay could detect down to a single molecule of methylated DNA in a high background of normal DNA (0.03%) with perfect specificity in control samples. We found that 60% of the cancer patients exhibited BRCA1 promoter hypermethylation at one point, although 24% lost hypermethylation during treatment. Multivariate survival analyses indicate that relapses are independent events and that hypermethylation and methylation conversion are independently correlated to longer relapse‐free survival. We present a highly sensitive and specific methylation‐specific quantitative PCR‐based liquid biopsy assay. BRCA1 promoter hypermethylation is frequently found in ovarian cancer and is often reversed upon recurrence, indicating the selection of therapy‐resistant clones and unfavorable clinical outcome.Maha ElazezyKatharina PrieskeLan KluweLeticia Oliveira‐FerrerSven PeineVolkmar MüllerLinn WoelberBarbara SchmalfeldtKlaus PantelSimon A. JoosseWileyarticleBRCA1ctDNAliquid biopsyMS‐qPCRNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENMolecular Oncology, Vol 15, Iss 12, Pp 3615-3625 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	BRCA1 ctDNA liquid biopsy MS‐qPCR Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	BRCA1 ctDNA liquid biopsy MS‐qPCR Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Maha Elazezy Katharina Prieske Lan Kluwe Leticia Oliveira‐Ferrer Sven Peine Volkmar Müller Linn Woelber Barbara Schmalfeldt Klaus Pantel Simon A. Joosse BRCA1 promoter hypermethylation on circulating tumor DNA correlates with improved survival of patients with ovarian cancer
description	Methylation of the BRCA1 promoter is an epigenetic gene expression regulator and is frequently observed in ovarian cancer; however, conversion of methylation status is thought to drive disease recurrence. Therefore, longitudinal monitoring of methylation status by liquid biopsy in cell‐free DNA may be a predictive marker. In total, 135 plasma samples were collected from 69 ovarian cancer patients before and during systemic treatment. Our liquid biopsy assay could detect down to a single molecule of methylated DNA in a high background of normal DNA (0.03%) with perfect specificity in control samples. We found that 60% of the cancer patients exhibited BRCA1 promoter hypermethylation at one point, although 24% lost hypermethylation during treatment. Multivariate survival analyses indicate that relapses are independent events and that hypermethylation and methylation conversion are independently correlated to longer relapse‐free survival. We present a highly sensitive and specific methylation‐specific quantitative PCR‐based liquid biopsy assay. BRCA1 promoter hypermethylation is frequently found in ovarian cancer and is often reversed upon recurrence, indicating the selection of therapy‐resistant clones and unfavorable clinical outcome.
format	article
author	Maha Elazezy Katharina Prieske Lan Kluwe Leticia Oliveira‐Ferrer Sven Peine Volkmar Müller Linn Woelber Barbara Schmalfeldt Klaus Pantel Simon A. Joosse
author_facet	Maha Elazezy Katharina Prieske Lan Kluwe Leticia Oliveira‐Ferrer Sven Peine Volkmar Müller Linn Woelber Barbara Schmalfeldt Klaus Pantel Simon A. Joosse
author_sort	Maha Elazezy
title	BRCA1 promoter hypermethylation on circulating tumor DNA correlates with improved survival of patients with ovarian cancer
title_short	BRCA1 promoter hypermethylation on circulating tumor DNA correlates with improved survival of patients with ovarian cancer
title_full	BRCA1 promoter hypermethylation on circulating tumor DNA correlates with improved survival of patients with ovarian cancer
title_fullStr	BRCA1 promoter hypermethylation on circulating tumor DNA correlates with improved survival of patients with ovarian cancer
title_full_unstemmed	BRCA1 promoter hypermethylation on circulating tumor DNA correlates with improved survival of patients with ovarian cancer
title_sort	brca1 promoter hypermethylation on circulating tumor dna correlates with improved survival of patients with ovarian cancer
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/d5b14d9287144f21a36580691214ee91
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BRCA1 promoter hypermethylation on circulating tumor DNA correlates with improved survival of patients with ovarian cancer

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