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TP53 Mutations in Serum Circulating Cell-Free Tumor DNA As Longitudinal Biomarker for High-Grade Serous Ovarian Cancer

The aim of this study was to determine an optimal workflow to detect TP53 mutations in baseline and longitudinal serum cell free DNA (cfDNA) from high-grade serous ovarian carcinomas (HGSOC) patients and to define whether TP53 mutations are suitable as biomarker for disease. TP53 was investigated in...

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Autores principales: Vitale, Silvia R., Groenendijk, Floris H., van Marion, Ronald, Beaufort, Corine M., Helmijr, Jean C., Jan Dubbink, Hendrikus, N. M. Dinjens, Winand, Ewing-Graham, Patricia C., Smolders, Ramon, van Doorn, Helena C., Boere, Ingrid A., Berns, Els M. J. J., Helleman, Jozien, Jansen, Maurice P. H. M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7175353/
https://www.ncbi.nlm.nih.gov/pubmed/32156073
http://dx.doi.org/10.3390/biom10030415
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author Vitale, Silvia R.
Groenendijk, Floris H.
van Marion, Ronald
Beaufort, Corine M.
Helmijr, Jean C.
Jan Dubbink, Hendrikus
N. M. Dinjens, Winand
Ewing-Graham, Patricia C.
Smolders, Ramon
van Doorn, Helena C.
Boere, Ingrid A.
Berns, Els M. J. J.
Helleman, Jozien
Jansen, Maurice P. H. M.
author_facet Vitale, Silvia R.
Groenendijk, Floris H.
van Marion, Ronald
Beaufort, Corine M.
Helmijr, Jean C.
Jan Dubbink, Hendrikus
N. M. Dinjens, Winand
Ewing-Graham, Patricia C.
Smolders, Ramon
van Doorn, Helena C.
Boere, Ingrid A.
Berns, Els M. J. J.
Helleman, Jozien
Jansen, Maurice P. H. M.
author_sort Vitale, Silvia R.
collection PubMed
description The aim of this study was to determine an optimal workflow to detect TP53 mutations in baseline and longitudinal serum cell free DNA (cfDNA) from high-grade serous ovarian carcinomas (HGSOC) patients and to define whether TP53 mutations are suitable as biomarker for disease. TP53 was investigated in tissue and archived serum from 20 HGSOC patients by a next-generation sequencing (NGS) workflow alone or combined with digital PCR (dPCR). AmpliSeq™-focused NGS panels and customized dPCR assays were used for tissue DNA and longitudinal cfDNAs, and Oncomine NGS panel with molecular barcoding was used for baseline cfDNAs. TP53 missense mutations were observed in 17 tissue specimens and in baseline cfDNA for 4/8 patients by AmpliSeq, 6/9 patients by Oncomine, and 4/6 patients by dPCR. Mutations in cfDNA were detected in 4/6 patients with residual disease and 3/4 patients with disease progression within six months, compared to 5/11 patients with no residual disease and 6/13 patients with progression after six months. Finally, mutations were detected at progression in 5/6 patients, but not during chemotherapy. NGS with molecular barcoding and dPCR were most optimal workflows to detect TP53 mutations in baseline and longitudinal serum cfDNA, respectively. TP53 mutations were undetectable in cfDNA during treatment but re-appeared at disease progression, illustrating its promise as a biomarker for disease monitoring.
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spelling pubmed-71753532020-04-28 TP53 Mutations in Serum Circulating Cell-Free Tumor DNA As Longitudinal Biomarker for High-Grade Serous Ovarian Cancer Vitale, Silvia R. Groenendijk, Floris H. van Marion, Ronald Beaufort, Corine M. Helmijr, Jean C. Jan Dubbink, Hendrikus N. M. Dinjens, Winand Ewing-Graham, Patricia C. Smolders, Ramon van Doorn, Helena C. Boere, Ingrid A. Berns, Els M. J. J. Helleman, Jozien Jansen, Maurice P. H. M. Biomolecules Article The aim of this study was to determine an optimal workflow to detect TP53 mutations in baseline and longitudinal serum cell free DNA (cfDNA) from high-grade serous ovarian carcinomas (HGSOC) patients and to define whether TP53 mutations are suitable as biomarker for disease. TP53 was investigated in tissue and archived serum from 20 HGSOC patients by a next-generation sequencing (NGS) workflow alone or combined with digital PCR (dPCR). AmpliSeq™-focused NGS panels and customized dPCR assays were used for tissue DNA and longitudinal cfDNAs, and Oncomine NGS panel with molecular barcoding was used for baseline cfDNAs. TP53 missense mutations were observed in 17 tissue specimens and in baseline cfDNA for 4/8 patients by AmpliSeq, 6/9 patients by Oncomine, and 4/6 patients by dPCR. Mutations in cfDNA were detected in 4/6 patients with residual disease and 3/4 patients with disease progression within six months, compared to 5/11 patients with no residual disease and 6/13 patients with progression after six months. Finally, mutations were detected at progression in 5/6 patients, but not during chemotherapy. NGS with molecular barcoding and dPCR were most optimal workflows to detect TP53 mutations in baseline and longitudinal serum cfDNA, respectively. TP53 mutations were undetectable in cfDNA during treatment but re-appeared at disease progression, illustrating its promise as a biomarker for disease monitoring. MDPI 2020-03-07 /pmc/articles/PMC7175353/ /pubmed/32156073 http://dx.doi.org/10.3390/biom10030415 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Vitale, Silvia R.
Groenendijk, Floris H.
van Marion, Ronald
Beaufort, Corine M.
Helmijr, Jean C.
Jan Dubbink, Hendrikus
N. M. Dinjens, Winand
Ewing-Graham, Patricia C.
Smolders, Ramon
van Doorn, Helena C.
Boere, Ingrid A.
Berns, Els M. J. J.
Helleman, Jozien
Jansen, Maurice P. H. M.
TP53 Mutations in Serum Circulating Cell-Free Tumor DNA As Longitudinal Biomarker for High-Grade Serous Ovarian Cancer
title TP53 Mutations in Serum Circulating Cell-Free Tumor DNA As Longitudinal Biomarker for High-Grade Serous Ovarian Cancer
title_full TP53 Mutations in Serum Circulating Cell-Free Tumor DNA As Longitudinal Biomarker for High-Grade Serous Ovarian Cancer
title_fullStr TP53 Mutations in Serum Circulating Cell-Free Tumor DNA As Longitudinal Biomarker for High-Grade Serous Ovarian Cancer
title_full_unstemmed TP53 Mutations in Serum Circulating Cell-Free Tumor DNA As Longitudinal Biomarker for High-Grade Serous Ovarian Cancer
title_short TP53 Mutations in Serum Circulating Cell-Free Tumor DNA As Longitudinal Biomarker for High-Grade Serous Ovarian Cancer
title_sort tp53 mutations in serum circulating cell-free tumor dna as longitudinal biomarker for high-grade serous ovarian cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7175353/
https://www.ncbi.nlm.nih.gov/pubmed/32156073
http://dx.doi.org/10.3390/biom10030415
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