Circulating tumor-derived DNA is shorter than somatic DNA in plasma

Moulière, Florent; Rosenfeld, Nitzan

doi:10.1073/pnas.1501321112

Cited by 132 publications

(103 citation statements)

References 22 publications

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“…Indeed detection of EGFR T790M mutant DNA in the circulation of cancer patients was improved by selecting for shorter DNA fragment lengths [26]. Comparisons of tumor tissue somatic DNA and ccfDNA mutation rate can be impacted by the application of different sequencing technologies and amplicon sizes [27, 28] as well as read depths and these technical issues may bias the data interpretation [22]. To avoid this pitfall we used a platform that is adapted to the detection of short DNA fragments found as circulating cell-free DNA.…”

Section: Discussionmentioning

confidence: 99%

Circulating cell-free DNA mutation patterns in early and late stage colon and pancreatic cancer

et al. 2017

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Cancer is a heterogeneous disease harboring diverse subclonal populations that can be discriminated by their DNA mutations. Environmental pressure selects subclones that ultimately drive disease progression and tumor relapse. Circulating cell-free DNA (ccfDNA) can be used to approximate the mutational makeup of cancer lesions and can serve as a marker for monitoring disease progression at the molecular level without the need for invasively acquired samples from primary or metastatic lesions. This potential for molecular analysis makes ccfDNA attractive for the study of clonal evolution and for uncovering emerging therapeutic resistance or sensitivity. We assessed ccfDNA from colon and pancreatic adenocarcinoma patients using next generation sequencing of 56 cancer-associated genes at the time of primary resectable disease and metastatic progression and compared this to the mutational patterns of the primary tumor. 28%-47% of non-synonymous mutations in the primary tumors were also detected in the ccfDNA whilst 71%-78% mutations found in ccfDNA were not detected in the primary tumors. ccfDNA collected at the time of progression harbored 3-5 new mutations not detected in ccfDNA at the earlier collection time points. We conclude that incorporation of ccfDNA analysis provides crucial insights into the changing molecular makeup of progressive colon and pancreatic cancer.

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Section: Discussionmentioning

confidence: 99%

Circulating cell-free DNA mutation patterns in early and late stage colon and pancreatic cancer

et al. 2017

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“…However, these markers have limited utility in clinical settings due to their low sensitivity and small range of dynamic change compared to the magnitude of change in tumor burden [7][8][9]. www.impactjournals.com/oncotarget Circulating tumor DNA (ctDNA) comprises singleor double-stranded DNA that likely originates from cancer cells through the process of necrosis and apoptosis, and ctDNA exists in the plasma or serum [10][11][12]. ctDNA contains specific tumor mutations (i.e., TP53, PIK3CA and ESR1) in the cell-free DNA fraction of a given patient [13].…”

Section: Introductionmentioning

confidence: 99%

WITHDRAWN: Prognostic value of circulating tumor DNA in breast cancers

Gui¹,

Chen²,

Xu³

et al. 2018

Oncotarget

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Circulating tumor DNA (ctDNA) comprises single-or double-stranded DNA that likely originates from cancer cells. The prognostic value of ctDNA detection in breast cancer patients is currently under debate. Here, we conducted the first comprehensive meta-analysis of the published literature on the prognostic relevance of ctDNA, in patients with early-and advanced-stage disease.The PubMed and Embase databases were searched for studies on ctDNA in breast cancer patients.The main outcomes analyzed were overall survival (OS) and disease-free survival (DFS) in early-stage breast cancer patients as well as progression-free survival (PFS) and OS in metastatic breast cancer patients. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using random and fixed-effects models. A total of 16 studies involving 2070 participants were identified as eligible for inclusion in our meta-analysis, and the results of the pooled analysis showed that the presence of ctDNA was significantly associated with poor OS (HR = 1.98; 95% CI: 1.38-2.83, P = 0.0002) and DFS/PFS (HR = 1.87; 95% CI: 1.35-2.60, P = 0.0002) in the total breast cancer population. Furthermore, subgroup analysis revealed that associations between the presence of ctDNA and the outcome endpoints (OS and PFS) were significant within the metastatic breast cancer patient group and in patients with TP53 or ESR1 mutations in ctDNA.The TP53 and ESR1 mutations in ctDNA are potential prognostic biomarkers and promising therapeutic targets for advanced breast cancer.www.impactjournals.com/oncotarget/

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“…The fact that dissimilar to genomic DNA, ctDNA is extremely fragmented around nucleosomes (approximately 150 base pairs in length) (Fig. 1), supports the hypothesis that ctDNA originates through cell necrosis or apoptosis [35,36]. The DNA of eukaryotic cells is coiling around histone protein complexes, shaping nucleosomes as the basic form of chromatin [37].…”

Section: Ctdna As a Liquid Biopsy Componentmentioning

confidence: 63%

Circulating tumor DNA (ctDNA) in the era of personalized cancer therapy

Khatami

Tavangar

2018

J Diabetes Metab Disord

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The heterogeneity of tumor is considered as a major difficulty to victorious personalized cancer medicine. There is an extremeneed of consistent response evaluation for in vivo tumor heterogeneity anditscoupledconflict mechanisms. In this occasion researchers will be able to keep pace withpredictive, preventive, personalized, and Participatory (P4) medicine for cancer managements. In fact tumor heterogeneity is a central part of cancer evolution,soin order to progress in understanding of the dynamics within a tumor some diagnostic apparatus should be improved. Latest molecular techniques like Next generation Sequencing (NGS) and ultra-deep sequencing could disclose some clones within a liquid tumor biopsy which mainly responsible of treatment resistance. Circulating tumor DNA (ctDNA) as a main component of liquid biopsy is agifted biomarker for cancer mutation tracking as well as profiling. Personalized medicine facilitate learning regarding to genetic pools of tumor and their possible respond to treatment which could be much easier by using of ctDNA.With this information, cliniciansarelooking forward to find the best strategies for prevention, screening, and treatment in the way of precision medicine. Currently, numerous clinical efficacy of such informative improved treatment are in hand. Here we represent the review of plasma-derived ctDNA studies use in personalized cancer managements.

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Circulating tumor-derived DNA is shorter than somatic DNA in plasma

Cited by 132 publications

References 22 publications

Circulating cell-free DNA mutation patterns in early and late stage colon and pancreatic cancer

Circulating cell-free DNA mutation patterns in early and late stage colon and pancreatic cancer

WITHDRAWN: Prognostic value of circulating tumor DNA in breast cancers

Circulating tumor DNA (ctDNA) in the era of personalized cancer therapy

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