Characterization of Plasma Cell-Free DNA Integrity Using Droplet-Based Digital PCR: Toward the Development of Circulating Tumor DNA-Dedicated Assays.

Autor:	Poulet G; Centre de Recherche des Cordeliers, INSERM, CNRS, Sorbonne Université, USPC, Université de Paris, Equipe labellisée Ligue Nationale Contre le Cancer, CNRS SNC 5096, Paris, France.; Eurofins-Biomnis, Specialized Medical Biology Laboratory, Lyon, France., Garlan F; Centre de Recherche des Cordeliers, INSERM, CNRS, Sorbonne Université, USPC, Université de Paris, Equipe labellisée Ligue Nationale Contre le Cancer, CNRS SNC 5096, Paris, France., Garrigou S; Centre de Recherche des Cordeliers, INSERM, CNRS, Sorbonne Université, USPC, Université de Paris, Equipe labellisée Ligue Nationale Contre le Cancer, CNRS SNC 5096, Paris, France., Zonta E; Centre de Recherche des Cordeliers, INSERM, CNRS, Sorbonne Université, USPC, Université de Paris, Equipe labellisée Ligue Nationale Contre le Cancer, CNRS SNC 5096, Paris, France., Benhaim L; Centre de Recherche des Cordeliers, INSERM, CNRS, Sorbonne Université, USPC, Université de Paris, Equipe labellisée Ligue Nationale Contre le Cancer, CNRS SNC 5096, Paris, France.; Department of Visceral and Surgical Oncology, Gustave Roussy, Villejuif, France., Carrillon MJ; Centre de Recherche des Cordeliers, INSERM, CNRS, Sorbonne Université, USPC, Université de Paris, Equipe labellisée Ligue Nationale Contre le Cancer, CNRS SNC 5096, Paris, France., Didelot A; Centre de Recherche des Cordeliers, INSERM, CNRS, Sorbonne Université, USPC, Université de Paris, Equipe labellisée Ligue Nationale Contre le Cancer, CNRS SNC 5096, Paris, France., Le Corre D; Centre de Recherche des Cordeliers, INSERM, CNRS, Sorbonne Université, USPC, Université de Paris, Equipe labellisée Ligue Nationale Contre le Cancer, CNRS SNC 5096, Paris, France., Mulot C; Centre de Recherche des Cordeliers, INSERM, CNRS, Sorbonne Université, USPC, Université de Paris, Equipe labellisée Ligue Nationale Contre le Cancer, CNRS SNC 5096, Paris, France.; CIC-EC4 URC, HEGP, Hôpitaux Universitaires Paris Ouest AP-HP, Paris, France., Nizard P; Centre de Recherche des Cordeliers, INSERM, CNRS, Sorbonne Université, USPC, Université de Paris, Equipe labellisée Ligue Nationale Contre le Cancer, CNRS SNC 5096, Paris, France., Ginot F; Adelis, ID-solutions, Labège, France., Boutonnet-Rodat A; Adelis, ID-solutions, Labège, France., Blons H; Centre de Recherche des Cordeliers, INSERM, CNRS, Sorbonne Université, USPC, Université de Paris, Equipe labellisée Ligue Nationale Contre le Cancer, CNRS SNC 5096, Paris, France.; Department of Oncology, European Georges-Pompidou Hospital, AP-HP, Paris Descartes University, Paris, France., Bachet JB; Centre de Recherche des Cordeliers, INSERM, CNRS, Sorbonne Université, USPC, Université de Paris, Equipe labellisée Ligue Nationale Contre le Cancer, CNRS SNC 5096, Paris, France.; Sorbonne Universités, UPMC Université, Paris, France.; Department of Hepato-gastroenterology, Groupe Hospitalier Pitié Salpêtrière, Paris, France.; AGEO (Association des Gastroentérologues Oncologues), Paris, France., Taïeb J; Centre de Recherche des Cordeliers, INSERM, CNRS, Sorbonne Université, USPC, Université de Paris, Equipe labellisée Ligue Nationale Contre le Cancer, CNRS SNC 5096, Paris, France.; Department of Oncology, European Georges-Pompidou Hospital, AP-HP, Paris Descartes University, Paris, France.; AGEO (Association des Gastroentérologues Oncologues), Paris, France., Zaanan A; Centre de Recherche des Cordeliers, INSERM, CNRS, Sorbonne Université, USPC, Université de Paris, Equipe labellisée Ligue Nationale Contre le Cancer, CNRS SNC 5096, Paris, France.; Department of Oncology, European Georges-Pompidou Hospital, AP-HP, Paris Descartes University, Paris, France., Geromel V; Eurofins-Biomnis, Specialized Medical Biology Laboratory, Lyon, France., Pellegrina L; Eurofins-Biomnis, Specialized Medical Biology Laboratory, Lyon, France., Laurent-Puig P; Centre de Recherche des Cordeliers, INSERM, CNRS, Sorbonne Université, USPC, Université de Paris, Equipe labellisée Ligue Nationale Contre le Cancer, CNRS SNC 5096, Paris, France.; Department of Oncology, European Georges-Pompidou Hospital, AP-HP, Paris Descartes University, Paris, France., Wang-Renault SF; Centre de Recherche des Cordeliers, INSERM, CNRS, Sorbonne Université, USPC, Université de Paris, Equipe labellisée Ligue Nationale Contre le Cancer, CNRS SNC 5096, Paris, France., Taly V; Centre de Recherche des Cordeliers, INSERM, CNRS, Sorbonne Université, USPC, Université de Paris, Equipe labellisée Ligue Nationale Contre le Cancer, CNRS SNC 5096, Paris, France.
Jazyk:	angličtina
Zdroj:	Frontiers in oncology [Front Oncol] 2021 May 06; Vol. 11, pp. 639675. Date of Electronic Publication: 2021 May 06 (Print Publication: 2021).
DOI:	10.3389/fonc.2021.639675
Abstrakt:	Background: Cellular-cell free-DNA (ccfDNA) is being explored as a diagnostic and prognostic tool for various diseases including cancer. Beyond the evaluation of the ccfDNA mutational status, its fragmentation has been investigated as a potential cancer biomarker in several studies. However, probably due to a lack of standardized procedures dedicated to preanalytical and analytical processing of plasma samples, contradictory results have been published. Methods: ddPCR assays allowing the detection of KRAS wild-type and mutated sequences ( KRAS p.G12V, pG12D, and pG13D) were designed to target different fragments sizes. Once validated on fragmented and non-fragmented DNA extracted from cancer cell lines, these assays were used to investigate the influence of the extraction methods on the non-mutated and mutated ccfDNA integrity reflected by the DNA integrity index (DII). The DII was then analyzed in two prospective cohorts of metastatic colorectal cancer patients (RASANC study n = 34; PLACOL study n = 12) and healthy subjects ( n = 49). Results and Discussion: Our results demonstrate that ccfDNA is highly fragmented in mCRC patients compared with healthy individuals. These results strongly suggest that the characterization of ccfDNA integrity hold great promise toward the development of a universal biomarker for the follow-up of mCRC patients. Furthermore, they support the importance of standardization of sample handling and processing in such analysis. Competing Interests: VT: Honoraria from Raindance Technologies and Boerhinger Ingehleim; cofounder emulseo; board emulseo. JT: Honoraria from Merck, Amgen, Roche, Pierre Fabre, MSD, Sanofi, and Lilly, Servier, and Astra-Zeneca. AZ: consulting and/or advisory boards for: Roche, Merck Serono, Amgen, Sanofi, and Lilly. PL-P: Honoraria and board: Amgen, Merck-Serono, Boehringer Ingelheim, Sanofi, Roche, and Lilly. HB: Honoraria Astra-Zeneca, BMS, MSD. JT: Honoraria from Merck, AMGEN, ROCHE, SIRTEX, BAXALTA, SANOFI, Lilly, and Servier. AZ: Consulting and/or advisory boards for Roche, Merck Serono, Amgen, Sanofi, and Lilly. GP, LP, and VG: Eurofins-Biomnis employee. FGa: Bio-Rad employee. AB and FGi were employed by company ADELIS. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Poulet, Garlan, Garrigou, Zonta, Benhaim, Carrillon, Didelot, Le Corre, Mulot, Nizard, Ginot, Boutonnet-Rodat, Blons, Bachet, Taïeb, Zaanan, Geromel, Pellegrina, Laurent-Puig, Wang-Renault and Taly.)
Databáze:	MEDLINE
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