Synthetic Circulating Cell-free DNA as Quality Control Materials for Somatic Mutation Detection in Liquid Biopsy for Cancer

Zhang, Rui; Peng, Rongxue; Gao, Peng; Jia, Shiyu; Yang, Xin; Ding, Jian; Han, Yanxi; Xie, Jiehong

doi:10.1373/clinchem.2017.272559

Cited by 35 publications

(16 citation statements)

References 38 publications

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“…Comparisons with paired tissue specimens should have the same characteristics. Some authors (89) suggest using synthetic controls that imitate the DNA in the patient's plasma [98].…”

Section: Quality Controlmentioning

confidence: 99%

Liquid biopsy in oncology: a consensus statement of the Spanish Society of Pathology and the Spanish Society of Medical Oncology

et al. 2019

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The proportion of cancer patients with tumours that harbour a potentially targetable genomic alteration is growing considerably. The diagnosis of these genomic alterations can lead to tailored treatment at the onset of disease or on progression and to obtaining additional predictive information on immunotherapy efficacy. However, in up to 25% of cases, the initial tissue biopsy is inadequate for precision oncology and, in many cases, tumour genomic profiling at progression is not possible due to technical limitations of obtaining new tumour tissue specimens. Efficient diagnostic alternatives are therefore required for molecular stratification, which includes liquid biopsy. This technique enables the evaluation of the tumour genomic profile dynamically and captures intra-patient genomic heterogeneity as well. To date, there are several diagnostic techniques available for use in liquid biopsy, each one of them with different precision and performance levels. The objective of this consensus statement of the Spanish Society of Pathology and the Spanish Society of Medical Oncology is to evaluate the viability and effectiveness of the different methodological approaches in liquid biopsy in cancer patients and the potential application of this method to current clinical practice. The experts contributing to this consensus statement agree that, according to current evidence, liquid biopsy is an acceptable alternative to tumour tissue biopsy for the study of biomarkers in various clinical settings. It is therefore important to standardise pre-analytical and analytical procedures, to ensure reproducibility and generate structured and accessible clinical reports. It is essential to appoint multidisciplinary tumour molecular boards to oversee these processes and to enable the most suitable therapeutic decisions for each patient according to the genomic profile.

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“…Comparisons with paired tissue specimens should have the same characteristics. Some authors (89) suggest using synthetic controls that imitate the DNA in the patient's plasma [98].…”

Section: Quality Controlmentioning

confidence: 99%

Liquid biopsy in oncology: a consensus statement of the Spanish Society of Pathology and the Spanish Society of Medical Oncology

et al. 2019

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“…The sheared DNA fragments, containing different variants, were prepared by PCR‐based site‐directed mutagenesis and ultrasonication. Further details of the preparation of synthetic ctDNA samples are described in our previous report . The primers used to construct each variant are listed in supplemental online Table 1.…”

Section: Methodsmentioning

confidence: 99%

From Somatic Variants Toward Precision Oncology: An Investigation of Reporting Practice for Next-Generation Sequencing-Based Circulating Tumor DNA Analysis

et al. 2019

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Background With the accelerated development of next‐generation sequencing (NGS), identified variants, and targeted therapies, clinicians who confront the complicated and multifarious genetic information may not effectively incorporate NGS‐based circulating tumor DNA (ctDNA) analysis into routine patient care. Consequently, standardized ctDNA testing reports are of vital importance. In an effort to guarantee high‐quality reporting performance, we conducted an investigation of the current detection and reporting practices for NGS‐based ctDNA analysis. Materials and Methods A set of simulated ctDNA samples with known variants at known allelic frequencies and a corresponding case scenario were distributed to 66 genetic testing laboratories for ctDNA analysis. Written reports were collected to evaluate the detection accuracy, reporting integrity, and information sufficiency using 21 predefined criteria. Results Current reporting practices for NGS‐based ctDNA analysis were found to be far from satisfactory, especially regarding testing interpretation and methodological details. Only 42.4% of laboratories reported the results in complete concordance with the expected results. Moreover, 74.2% of reports only listed aberrations with direct and well‐known treatment consequences for the tumor type in question. Genetic aberrations for which experimental agents and/or drug access programs are available may thus be overlooked. Furthermore, methodological details for the interpretation of results were missing from the majority of reports (87.9%). Conclusion This proof‐of‐principle study suggests that the capacity for accurate identification of variants, rational interpretation of genotypes, comprehensive recommendation of potential medications, and detailed description of methodologies need to be further improved before ctDNA analysis can be formally implemented in the clinic. Implications for Practice Accurate, comprehensive, and standardized clinical sequencing reports can help to translate complex genetic information into patient‐centered clinical decisions, thereby shepherding precision oncology into daily practice. However, standards, guidelines, and quality requirements for clinical reports of next‐generation sequencing (NGS)‐based circulating tumor DNA (ctDNA) analysis are currently absent. By using a set of simulated clinical ctDNA samples and a corresponding case scenario, current practices were evaluated to identify deficiencies in clinical sequencing reports of ctDNA analysis. The recommendations provided here may serve as a roadmap for the improved implementation of NGS‐based ctDNA analysis in the clinic.

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“…The remaining three K2-EDTA containers were stored at 4˚C for 48 hr. The performance of cfDNA extraction was compared between plasma samples obtained by immediate centrifugation after blood draw and those with delayed centrifugation (6,24, and 48 hr) of refrigerated whole blood (Fig. 1B).…”

Section: Study Design and Sample Collectionmentioning

confidence: 99%

“…The EGFR test results with the semi-quantitative index (SQI) of the cfDNA specimens extracted from each patient according to the specimen container type and storage conditions are described in Recently, quality control material for cfDNA analysis has been reported [24], and efforts to improve the quality of cfDNA-related tests are expected to continue.…”

Section: Egfr Gene Mutation Analysismentioning

confidence: 99%

Effects of Pre-analytical Variables on Cell-free DNA Extraction for Liquid Biopsy

et al. 2019

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mutations using circulating cell-free DNA (cfDNA). It is well known that, unlike invasive tissue biopsy, one advantage of liquid biopsies is the evaluation of cancer-related gene mutations through blood sampling, which is a minimally invasive technique [1-4]. In addition, tissue biopsies are dif cult to perform repeatedly, and complications related to the procedure may occur depending on the site of the biopsy organ [5-7]. Above all, tumor heterogeneity is a signi cant challenge when detecting genetic alteration of tumors by tissue biopsy [5, 8, 9]. In contrast, liquid biopsy can be performed easily and repeatedly through blood collection. Since DNA is released into the blood vessels from the tumor tissue, another advantage of liquid biopsies is that it can reect the real-time genetic characteristics of the tumor [5-9]. The cfDNA is rapidly degraded by nucleases in circulating blood [10, 11], and delayed plasma separation can lead to contam

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Synthetic Circulating Cell-free DNA as Quality Control Materials for Somatic Mutation Detection in Liquid Biopsy for Cancer

Abstract: BACKGROUND:Detection of somatic genomic alterations in tumor-derived cell-free DNA (cfDNA) in the plasma is challenging owing to the low concentrations of cfDNA, variable detection methods, and complex workflows. Moreover, no proper quality control materials are available currently.

Cited by 35 publications

References 38 publications

Liquid biopsy in oncology: a consensus statement of the Spanish Society of Pathology and the Spanish Society of Medical Oncology

Liquid biopsy in oncology: a consensus statement of the Spanish Society of Pathology and the Spanish Society of Medical Oncology

From Somatic Variants Toward Precision Oncology: An Investigation of Reporting Practice for Next-Generation Sequencing-Based Circulating Tumor DNA Analysis

Effects of Pre-analytical Variables on Cell-free DNA Extraction for Liquid Biopsy

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