Journal
FRONTIERS IN ONCOLOGY
Volume 11, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2021.639675
Keywords
circulating tumor DNA; picoliter-droplet digital PCR; cancer biomarker; apoptosis; necrosis; DNA integrity index; circulating cell-free DNA
Categories
Funding
- Ministere de l'Enseignement Superieur et de la Recherche
- Universite Paris-Descartes
- Centre National de la Recherche Scientifique (CNRS)
- Institut National de la Sante et de la Recherche Medicale (INSERM)
- Institut National du Cancer (INCA) [2009-1-RT-03-US-1, 2009-RT-03-UP5-1]
- Association pour la recherche contre le cancer (ARC) [SL220100601375]
- Agence Nationale de la Recherche (ANR Nanobiotechnologies) [ANR-10-NANO-0002-09]
- SIRIC CARPEM
- ligue nationale contre le cancer (LNCC, Program Equipe labelisee LIGUE) [EL2016.LNCC/VaT]
- Advanced Merieux Research Grant
- CIFRE funding from the Association Nationale Recherche Technologie (ANRT) [2018/0368]
- Fondation Servier
- Eurofins-Biomnis
- AGEO
- AGEO Group
- Merck Serono s.a.s. (France), an affiliate of Merck KGaA (Darmstadt, Germany)
- Agence Nationale de la Recherche (ANR) [ANR-10-NANO-0002] Funding Source: Agence Nationale de la Recherche (ANR)
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Research has shown that ccfDNA is highly fragmented in metastatic colorectal cancer patients compared to healthy individuals. These results strongly suggest that characterizing ccfDNA integrity holds great promise for developing a universal biomarker for the follow-up of mCRC patients. Furthermore, the results support the importance of standardizing sample handling and processing in such analysis.
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.
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