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Open AccessArticle

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

1
Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, 3015 CN Rotterdam, The Netherlands
2
Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy
3
Center of Experimental Oncology and Hematology, A.O.U. Policlinico-Vittorio Emanuele, 95123 Catania, Italy
4
Department of Pathology, Erasmus MC Cancer Institute, Erasmus University Medical Center, 3015 CN Rotterdam, The Netherlands
5
Department of Gynaecology, Erasmus MC Cancer Institute, Erasmus University Medical Center, 3015 CN Rotterdam, The Netherlands
*
Author to whom correspondence should be addressed.
Biomolecules 2020, 10(3), 415; https://doi.org/10.3390/biom10030415
Received: 19 December 2019 / Revised: 6 February 2020 / Accepted: 5 March 2020 / Published: 7 March 2020
(This article belongs to the Special Issue Recent Advances in p53)
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. View Full-Text
Keywords: ovarian cancer; TP53; cell-free DNA; serum; dPCR; next-generation sequencing; molecular barcoding ovarian cancer; TP53; cell-free DNA; serum; dPCR; next-generation sequencing; molecular barcoding
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Vitale, S.R.; Groenendijk, F.H.; van Marion, R.; Beaufort, C.M.; Helmijr, J.C.; Jan Dubbink, H.; N. M. Dinjens, W.; Ewing-Graham, P.C.; Smolders, R.; van Doorn, H.C.; Boere, I.A.; Berns, E.M.J.J.; Helleman, J.; Jansen, M.P.H.M. TP53 Mutations in Serum Circulating Cell-Free Tumor DNA As Longitudinal Biomarker for High-Grade Serous Ovarian Cancer. Biomolecules 2020, 10, 415.

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