Circulating tumor DNA identified by targeted sequencing in advanced-stage non-small cell lung cancer patients

Xu, Song; Feng, Li; Wu, Yi Lin; Sun, Di; Zhang, Jingbo; Chen, Wei; Ye, Hua; Li, Jian‐Rong; Wei, Sen; Zhao, Mingyu; Wu, Wenjun; Su, Xue-Xia; Shi, Rong; Jones, Lindsey; Huang, Xue F.; Chen, Si-Yi; Chen, Jun

doi:10.1016/j.canlet.2015.11.005

Cited by 98 publications

(89 citation statements)

References 37 publications

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“…For example, in a proof‐of‐concept study, the FDA‐approved Oncomine targeted sequencing kit demonstrated a sensitivity of only 77% for the detection of sensitizing EGFR mutations in cfDNA of NSCLC patients . Similar results, with an overall concordance of 76% between tumor tissue and cfDNA, were reported for the AmpliSeq Cancer Panel . To overcome these limitations, more sensitive targeted and genome‐wide sequencing approaches with improved error suppression rates have been developed .…”

Section: Different Methods For Mutation Detection In Routine Diagnosticsmentioning

confidence: 71%

A field guide for cancer diagnostics using cell‐free DNA: From principles to practice and clinical applications

Volckmar

Sültmann

Riediger

et al. 2017

Genes Chromosomes & Cancer

169

151

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Recently, many genome-wide profiling studies provided insights into the molecular make-up of major cancer types. The deeper understanding of these genetic alterations and their functional consequences led to the discovery of novel therapeutic opportunities improving clinical management of cancer patients. While tissue-based molecular patient stratification is the gold standard for precision medicine, it has certain limitations: Tissue biopsies are invasive sampling procedures carrying the risk of complications and may not represent the entire tumor due to underlying genetic heterogeneity. In this context, complementary characterization of genetic information in the blood of cancer patients can serve as minimal-invasive 'liquid biopsy'. Fragments of circulating cell-free DNA (cfDNA) are released from tissues of healthy individuals as well as cancer patients. The fraction of cfDNA that is released from primary tumors or metastases (i.e. circulating tumor DNA, ctDNA) represents genetic aberrations in cancer cells, which are a potential source for diagnostic, prognostic, and predictive biomarkers. Recent studies have demonstrated technical feasibility and clinical applications including detection of drug targets and resistance mutations as well as longitudinal monitoring of tumors under therapy. To this end, a variety of pre-analytical procedures for blood processing, isolation and quantification of cfDNA are being employed and several analytical methods and technologies ranging from PCR-based single locus assays to genome-wide approaches are available, which considerably differ in sensitivity, specificity, and throughput. However, broad implementation of ctDNA analysis in daily clinical practice requires a thorough understanding of theoretical, technical, and biological concepts and necessitates standardization and validation of pre-analytical and analytical procedures across different technologies. Here, we review the pertinent literature and discuss the advantages and limitations of available methodologies and their potential applications in molecular diagnostics.

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Section: Different Methods For Mutation Detection In Routine Diagnosticsmentioning

confidence: 71%

A field guide for cancer diagnostics using cell‐free DNA: From principles to practice and clinical applications

Volckmar

Sültmann

Riediger

et al. 2017

Genes Chromosomes & Cancer

169

151

View full text Add to dashboard Cite

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“…Xu et al. () reported a consistency of 76.2% for next‐generation sequencing technology in detecting gene mutation in tissue samples and cell‐free DNA of paired blood samples in advanced lung cancer patients. We found a consistency of 76.2% for TP53 and 95.24% for BRCA1 in circulating tumor‐free DNA and tumor tissue DNA, suggesting that cell‐free DNA and circulating tumor cells could offer a ready and convenient source for liquid biopsy for detection of biomarkers that could be used to monitor disease development and predict prognosis.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, circulating cell‐free DNA and circulating tumor cells have been found to offer a ready and convenient source for liquid biopsy (Xu et al., ); genetic alterations found in liquid biopsy specimens are identical to those in primary cancer tissues. Murtaza et al.…”

Section: Introductionmentioning

confidence: 99%

Next‐generation sequencing unravels extensive genetic alteration in recurrent ovarian cancer and unique genetic changes in drug‐resistant recurrent ovarian cancer

Wang

et al. 2018

Molec Gen & Gen Med

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BackgroundBy using a high‐throughput sequencing technique, we sought to delineate genetic alterations in recurrent ovarian cancer patients and further compare genetic changes in drug‐resistant and ‐sensitive recurrent ovarian cancer patients. We also sought to study the specificity, sensitivity, and consistency of DNA biomarkers in liquid biopsy specimens and ovarian cancer tissue DNA.MethodsTumor tissue specimens and blood samples were obtained from pathologically proven recurrent ovarian cancer patients. Genomic DNA was extracted from tumor tissues, blood cells, ascites, and urine samples. The DNA Library was constructed and sequencing was performed using the Illumina HiSeq 4000 high‐throughput sequencing platform. Bioinformatic analysis was done using the Torrent Suite software.ResultsTen patients with pathologically proven drug‐resistant recurrent ovarian cancer and 11 patients with sensitive recurrent ovarian cancer were included. The 5‐year OS for drug‐resistant recurrent ovarian cancer patients (44 ± 11.07 months, 95% CI: 231.24–53.66 months) was significantly lower than that of drug‐sensitive recurrent ovarian cancer patients (58 ± 3.97 months; 95% CI: 50.05–65.59 months; p = 0.024) TP53 was the most frequently mutated gene in both drug‐resistant (9/10, 90%) and drug‐sensitive recurrent ovarian cancers (10/11, 91%). MYC and RB1 had the highest frequency of copy number variations (6/21, 29%) in recurrent ovarian cancers, followed by PIK3CA (3/21, 14%). BRCA2 N372H polymorphism was found in 40% (4/10) of drug‐resistant recurrent ovarian cancer patients. The specificity, sensitivity, and consistency of TP53 and BRCA1 in circulating tumor‐free DNA and tumor tissue DNA were 100%, 73.7%, 76.2% and 100%, 75%, 95.24%, respectively.ConclusionWe uncovered extensive genetic alterations in recurrent ovarian cancer and drug‐resistant recurrent ovarian cancer exhibited unique genetic changes compared with recurrent ovarian cancer and drug‐sensitive recurrent ovarian cancer. We further showed that high‐throughput sequencing using liquid biopsy specimens could provide an effective, specific, and sensitive approach for detecting genetic alterations in ovarian cancer.

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“…ctDNA can be applied in detection of point mutations, copy number variation (CNV), rearrangements, microsatellite instability (MSI), loss of heterozygosity (LOH) and DNA methylation . Multiple studies have shown that the mutation profile detected by ctDNA has a good concordance with paired tumor tissues, with 70% in lung cancer and 39%–55% in colorectal and rectal cancer . ctDNA analysis also facilitates the assessment of intra‐patient multiple drug resistance mechanisms caused by tumor heterogeneity in non‐small cell lung cancer (NSCLC) .…”

mentioning

confidence: 99%

Circulating tumor DNA functions as an alternative for tissue to overcome tumor heterogeneity in advanced gastric cancer

et al. 2017

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Overcoming tumor heterogeneity is a major challenge for personalized treatment of gastric cancer, especially for human epidermal growth factor receptor‐2 targeted therapy. Analysis of circulating tumor DNA allows a more comprehensive analysis of tumor heterogeneity than traditional biopsies in lung cancer and breast cancer, but little is known in gastric cancer. We assessed mutation profiles of ctDNA and primary tumors from 30 patients with advanced gastric cancer, then performed a comprehensive analysis of tumor mutations by multiple biopsies from five patients, and finally analyzed the concordance of HER2 amplification in ctDNA and paired tumor tissues in 70 patients. By comparing with a single tumor sample, ctDNA displayed a low concordance of mutation profile, only approximately 50% (138/275) somatic mutations were found in paired tissue samples, however, when compared with multiple biopsies, most DNA mutations in ctDNA were also shown in paired tumor tissues. ctDNA had a high concordance (91.4%, Kappa index = 0.784, P < 0.001) of HER2 amplification with tumor tissues, suggesting it might be an alternative for tissue. It implied that ctDNA‐based assessment could partially overcome the tumor heterogeneity, and might serve as a potential surrogate for HER2 analysis in gastric cancer.

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Circulating tumor DNA identified by targeted sequencing in advanced-stage non-small cell lung cancer patients

Cited by 98 publications

References 37 publications

A field guide for cancer diagnostics using cell‐free DNA: From principles to practice and clinical applications

A field guide for cancer diagnostics using cell‐free DNA: From principles to practice and clinical applications

Next‐generation sequencing unravels extensive genetic alteration in recurrent ovarian cancer and unique genetic changes in drug‐resistant recurrent ovarian cancer

Circulating tumor DNA functions as an alternative for tissue to overcome tumor heterogeneity in advanced gastric cancer

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